Impact of antigen loading in tolerogenic nanoparticles to mitigate Th2-mediated allergic lung inflammation.

Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies.

Interleukin antagonists for atopic dermatitis: a new era of therapy.

INTRODUCTION: Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab and the IL-13 inhibitor tralokinumab have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development. AREAS COVERED: In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD. EXPERT OPINION: Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

Investigating the role of vitamin D in asthma.

Results in mice suggest that vitamin D reduces the symptoms of asthma by controlling an immune response that leads to inflammation of the airways.

Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

Mycobacterium tuberculosis EspR modulates Th1-Th2 shift by transcriptionally regulating IL-4, steering increased mycobacterial persistence and HIV propagation during co-infection.

Mycobacterium tuberculosis (Mtb) and HIV are known to mutually support each other during co-infection by multiple mechanisms. This synergistic influence could be either by direct interactions or indirectly through secreted host or pathogen factors that work in trans. Mtb secretes several virulence factors to modulate the host cellular environment for its persistence and escaping cell-intrinsic immune responses. We hypothesized that secreted Mtb transcription factors that target the host nucleus can directly interact with host DNA element(s) or HIV LTR during co-infection, thereby modulating immune gene expression, or driving HIV transcription, helping the synergistic existence of Mtb and HIV. Here, we show that the Mtb-secreted protein, EspR, a transcription regulator, increased mycobacterial persistence and HIV propagation during co-infection. Mechanistically, EspR localizes to the nucleus of the host cells during infection, binds to its putative cognate motif on the promoter region of the host IL-4 gene, activating IL-4 gene expression, causing high IL-4 titers that induce a Th2-type microenvironment, shifting the macrophage polarization to an M2 state as evident from CD206 dominant population over CD64. This compromised the clearance of the intracellular mycobacteria and enhanced HIV propagation. It was interesting to note that EspR did not bind to HIV LTR, although its transient expression increased viral propagation. This is the first report of an Mtb transcription factor directly regulating a host cytokine gene. This augments our understanding of the evolution of Mtb immune evasion strategies and unveils how Mtb aggravates comorbidities, such as HIV co-infection, by modulating the immune microenvironment.

Synergy between Th1 and Th2 responses during endometriosis: A review of current understanding.

Endometriosis is widely perceived as an estrogen-dependent chronic disorder with infertility and pelvic pain. Although the etiology of endometriosis has remained elusive, many studies have proclaimed the relevance of immune system disorders with endometriosis. With the discovery that the dysregulation of multiple biological functions in endometriosis is caused by the aberrant differentiation of T helper cells, a shift towards Th2 immune response may account for the disease progression. This review attempts to present mechanisms of cytokines, chemokines, signal pathways, transcription factors and some other factors related with the derivation of Th1/Th2 immune response involved in the development of endometriosis. The current understanding of treatment approaches and potential therapeutic targets will also be outlined with brief discussion.

Pathogenesis of Nasal Polyposis: Current Trends.

Chronic Rhinosinusitis (CRS) is characterized by edema of the sub-epithelial layers, but, only specific types of CRS are developing polyps. Nasal polyposis may develop under different pathogenetic mechanisms rendering the typical macroscopic classification of CRS, with or without nasal polyps, rather deficient. Currently, we approach nasal polyposis, in terms of diagnosis and treatment, according to its endotype, which means that we focus on the specific cells and cytokines that are participating in its pathogenesis. It appears that the molecular procedures that contribute to polyp formation, initiating with a Th-2 response of the adaptive immune system, are local phenomena occurring in the sub-epithelial layers of the mucosa. Several hypotheses are trying to approach the etiology that drives the immune response towards Th-2 type. Extrinsic factors, like fungi, Staphylococcus superantigens, biofilms, and altered microbiome can contribute to a modified and intense local reaction of the immune system. Some hypotheses based on intrinsic factors like the elimination of Treg lymphocytes, low local vitamin-D levels, high levels of leukotrienes, epithelial to mesenchymal transition (EMT) induced by hypoxia, and altered levels of NO, add pieces to the puzzle of the pathogenesis of nasal polyposis. Currently, the most complete theory is that of epithelial immune barrier dysfunction. Intrinsic and extrinsic conditions can damage the epithelial barrier rendering sub-epithelial layers more vulnerable to invasion by pathogens that trigger a Th-2 response of the adaptive immune system. Th2 cytokines, subsequently, induce the accumulation of eosinophils and IgE together with the remodeling of the stroma in the sub-epithelial layers leading, eventually, to the formation of nasal polyps.

Peptide ILE-GLU-TRP (Stemokin) Potential Adjuvant Stimulating a Balanced Immune Response.

Vaccines are widely used worldwide to prevent and protect from various infections. A variety of modern approaches to developing prophylactic and therapeutic vaccines is growing. In almost all cases, adjuvants are necessary to obtain an effective immune response.This work investigated the possibility of using the pharmaceutical peptide drug Stemokin as an adjuvant stimulating a balanced Th1/Th2 response.A study was conducted to compare the activity of Stemokin versus the approved adjuvant Alhydrogel in a murine vaccination model with the approved VAXIGRIP® vaccine.The first proof-of-concept experimental study shows that the peptide Ile-Glu-Trp has the adjuvant vaccine properties and anti-HA IgG2a enhancing response, revealing a Th1- favoring balanced Th1/Th2 immunomodulation.

The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review.

In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the principal signaling cascade for a large number of cytokines and growth factors and is involved in intracellular signal transduction and subsequent regulation of gene transcription. Current knowledge suggests that the robust activation of the T-helper (Th)-2 [interleukin (IL)-4, IL-5, IL-13, IL-31] and Th22 (IL-22) immune responses in both skin and serum plays a pivotal role in the immunopathogenesis of AD especially at the acute stage, followed by a variable degree of Th1 (interferon-γ, tumor necrosis factor alpha) and Th17 (IL-17) activation in chronic disease. Of note, most of the aforementioned inflammatory cytokines utilize the JAK/STAT pathway for downstream signal transduction, explaining the emerging role of JAK inhibitors in the therapeutic armamentarium of AD. The present systematic review aims to discuss the involvement of JAK/STAT pathway in the pathogenesis of AD and summarize the clinical data available on the efficacy and safety of JAK inhibitors which have been used in the treatment of AD thus far.

Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s.

The role of Dectin-2 (gene symbol, Clec4n) in house dust mite (HDM) induced Th2 immune response and the exact mechanism remains controversial. In this study, we illustrated that, Clec4n-/- mice had decreased Th2 immune response following HDM challenge, which may ascribe to dramatically reduced type 2 conventional dendritic cells (cDC2s) in lung of Clec4n-/- mice, as cDC2s from lung of Clec4n-/- mice after challenging had less ability to induce Th2 response with decreased production of IL-4/IL-13. Further in vitro experiments showed the activation of Clec4n-/--BMDCs significantly decreased after HDM stimulation accompanied with decreased activation of Syk-NF-κB and Syk-JNK signal pathway. Importantly, Dectin-2 expression in PBMCs from asthmatic patients was significantly higher than that in healthy controls. Taken together, these results demonstrated that Dectin-2 could promote cDC2s activation in lung, which polarizes Th2 immune response outlining a novel mechanism of asthma development.

Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis.

AIM: To investigate the potential interactions of thymic stromal lymphopoietin (TSLP) with interleukin-4 (IL-4) in adaptive immunity during fungal keratitis (FK). METHODS: An FK mouse model was induced with Aspergillus fumigatus (AF) hyphal infection. Mice were divided into several groups: untreated, phosphate buffer saline (PBS), infected with AF, and pretreated with a scrambled siRNA, a TSLP-specific siRNA (TSLP siRNA), murine recombinant TSLP (rTSLP), immunoglobulin G (IgG), murine recombinant IFN (rIFN-γ), murine recombinant IL-4 (rIL-4), rIL-13, murine recombinant IL-17A (rIL-17A), and murine recombinant IL-17F (rIL-17F) groups. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) or Western blot were performed to determine mRNA and protein levels in the inflamed cornea. Cytokine locations were observed by immunofluoresence staining after AF hyphal infection. RESULTS: Compared to those in the untreated group, TSLP and T helper type 1 (Th1) cytokine levels in the AF group were upregulated at 24h post infection (hpi), and those of T helper type 2 (Th2) and T helper type 17 (Th17) cytokines were increased at 5d post infection (dpi). Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group. The TSLP level was increased in the rIL-4-pretreated group, but there were no significant changes among the other groups. Immunofluorescence staining showed cytokine locations after AF hyphal infection. CONCLUSION: TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo. IL-4 promotes TSLP secretion. Therefore, TSLP with IL-4 regulates adaptive immunity in FK.

The Pathogenesis of Eosinophilic Asthma: A Positive Feedback Mechanism That Promotes Th2 Immune Response via Filaggrin Deficiency.

Eosinophilic asthma (EA) is a common subtype of asthma and often progresses to severe disease. In order to understand its pathogenesis, targeted next-generation gene sequencing was performed on 77 Chinese EA patients and 431 Chinese healthy controls to obtain differential genomic variations. Among the 41 Single Nucleotide Polymorphisms (SNPs) screened for mutation sites in more than 3 patients, filaggrin gene FLG rs192116923 T>G and FLG rs75235053 C>G were newly found to be associated with EA patients with atopic dermatitis (AD) (P <0.001) and severe EA (P=0.032), respectively. Filaggrin has been shown to be mainly expressed in epithelial cells and plays an important role in formation of an effective skin barrier. Bioinformatic analysis indicated FLG rs192116923 T>G may increase the binding of Smad3 to transmit TGF-ß1 signaling, and thereby inhibit filaggrin expression, and FLG rs75235053 C>G may add new splicing sites to reduce filaggrin monomers. It has been known that the level of Th2 cytokine IL-4 is increased in EA patients, and IL-4 increases airway epithelial permeability and enhances inflammatory response through some unclear mechanisms. To figure out whether filaggrin is involved in immune responses in asthma, we have treated human respiratory epithelial cell line BEAS-2B cells with IL-4 and found that the expression levels of filaggrin and E-cadherin decreased significantly in a time and dose-dependent manner, suggesting that IL-4 increased airway epithelial permeability by reducing filaggrin and adhesion molecule. In addition, in our study, IL-4 increased the expression of epithel-derived inflammatory cytokines IL-33 and TSLP which further enhanced the Th2 inflammatory response. To investigate the role of filaggrin in development of EA, knockdown filaggrin with siRNA revealed a decrease in E-cadherin levels, which were further down-regulated by IL-4 stimulation. Knockdown of filaggrin alone did not affect the levels of IL-33 and TSLP, but further exacerbated the decrease of IL-33/TSLP caused by IL-4, suggesting that filaggrin may involve in IL-4R signaling pathway to regulate the level of IL-33/TSLP. In conclusion, in the Th2 cytokine milieu of asthma, FLG deficient mutation in airway epithelial cells may increase the epithelial permeability and the expression of IL-33/TSLP which positively feedback the Th2 inflammation response.

Generation and Characterization of Torudokimab (LY3375880): A Monoclonal Antibody That Neutralizes Interleukin-33.

BACKGROUND: Interleukin-33 (IL-33) is an alarmin that is released following cellular damage, mechanical injury, or necrosis. It is a member of the IL-1 family and binds to a heterodimer receptor consisting of ST2 and IL-1RAP to induce the production of a wide range of cellular mediators, including the type 2 cytokines IL-4, IL-5 and IL-13. This relationship has led to the hypothesis that the IL-33/ST2 pathway is a driver of allergic disease and inhibition of the IL-33 and ST2 association could have therapeutic benefit. METHODS: In this paper, we describe the selection of a phage antibody through the ability to bind human IL-33 and block IL-33/ST2 interaction. This hit antibody was then affinity matured by site-directed mutagenesis of the antibody complementarity-determining regions (CDRs). Further characterization of a fully human monoclonal antibody (mAb), torudokimab (LY3375880) included demonstration of human IL-33 neutralization activity in vitro with an NFκB reporter assay and IL-33 induced mast cell cytokine secretion assay, followed by an in vivo IL-33-induced pharmacodynamic inhibition assay in mice that used IL-5 production as the endpoint. RESULTS: Torudokimab is highly specific to IL-33 and does not bind any of the other IL-1 family members. Furthermore, torudokimab binds human and cynomolgus monkey IL-33 with higher affinity than the binding affinity of IL-33 to ST2, but does not bind mouse, rat, or rabbit IL-33. Torudokimab's half-life in cynomolgous monkey projects monthly dosing in the clinic. CONCLUSION: Due to torudokimab's high affinity, its ability to completely neutralize IL-33 activity in vitro and in vivo, and the observed cynomolgus monkey pharmacokinetic properties, this molecule was selected for clinical development.

Lymphatic filariasis and visceral leishmaniasis coinfection: A review on their epidemiology, therapeutic, and immune responses.

Coinfection is less commonly observed in individuals around the world, yet it is more common than the single infection. Around 800 million people worldwide are infected with helminths as a result of various diseases. Lymphatic filariasis (LF) and visceral leishmaniasis (VL) are chronic, deadly, crippling, and debilitating neglected tropical diseases (NTDs) that are endemic in tropical and subtropical regions of the world. Due to poor hygienic conditions, poverty, and genetic predisposition, those living in endemic areas are more likely to develop both leishmaniasis and filariasis. One of the key challenges in the management of LF/VL coinfection is the development of an effective therapeutic strategy that not only treats the first episode of VL but also prevents LF. However, there is a scarcity of knowledge and data on the relationship between LF and VL coinfection. While reviewing it was apparent that only a few studies relevant to LF/VL coinfections have been reported from southeastern Spain, Sudan, and the Indian subcontinents, highlighting the need for greater research in the most affected areas. We also looked at LF and VL as a single disease and also as a coinfection. Some features of the immune response evolved in mammalian hosts against LF and VL alone or against coinfection are also discussed, including epidemiology, therapeutic regimens, and vaccines. In addition to being potentially useful in clinical research, our findings imply the need for improved diagnostic methodology and therapeutics, which could accelerate the deployment of more specific and effective diagnosis for treatments to lessen the impact of VL/LF coinfections in the population.

Cross-protective efficacy of immuno-stimulatory recombinant Brugia malayi protein HSP60 against the Leishmania donovani in BALB/c mice.

Coinfection of Leishmania with bacteria, viruses, protozoans, and nematodes alter the immune system of the host, thereby influencing the disease outcomes. Here, we have determined the immunogenic property and protective efficacy of the cross-reactive molecule HSP60 of filarial parasite B. malayi against the L. donovani in BALB/c mice. Parasitological parameters results showed a significant decrease in the parasite burden (~59%; P < 0.001) and also a substantial increase in the delayed-type hypersensitivity (DTH) response (P < 0.001) in mice immunized with 10 µg of rBmHSP60. Protection against L. donovani in mice immunized with rBmHSP60 resulted from activation of the T cells, which is characterized by higher levels of nitric oxide (NO) production, enhanced cell proliferation, higher levels (expression and release) of IFN- γ, TNF- α, and IL-12, also, higher production of IgG and IgG2a antibodies. This strong Th1 immune response creates an inflammatory domain for L. donovani and protects the host from VL.

COVID-19 and pregnancy: are they friends or enemies?

OBJECTIVES: Novel coronavirus disease (COVID-19) is rapidly spreading all over the world. Although in many cases the infection causes very weak symptoms, it can be severe in patient with diverse chronical diseases and immunological compromising patients. Pregnancy is a unique condition in which mother and fetus peacefully collaborate. Diverse endocrine-immune mechanisms, mostly under progesterone control work together to protect the fetus from maternal immunocompetent cell activation driven rejection. The physiological shift to Th2 dominant environment, while favourable for fetus, it makes mothers susceptible to infective pathogens, making pregnancy during COVID-19 pandemic challenging. MATERIALS AND METHODS: Studies involving COVID-19 in pregnancy and those analysing changes of immune system induced by COVID-19 were searched in databases such as PubMed, Scopus, Google Scholar and ScienceDirect. Databases were searched using a keyword COVID-19/coronavirus, that was combined with following terms: immune system, pregnancy, oestrogen, or progesterone. Search included studies published up to 01.07.2020. Almost 1,500 articles were found, but only 18 met criteria. RESULTS: Most frequent symptoms of COVID-19 in mothers infected in the late pregnancy were fever and cough accompanied with lymphopenia and elevated C-reactive protein. Mothers reported to have severe disease had comorbidities and were obese. Low rate of neonatal complications of maternal Sars-Coc-2 infection without neonatal mortality was observed. CONCLUSIONS: Currently available data didn't show significant relationship between COVID-19 severity and pregnancy and there is no strong evidence that mother's infection can lead to adverse pregnancy outcome, but further studies are needed to determinate the possible effects of COVID-19 gained during earlier pregnancy.

DZNep attenuates allergic airway inflammation in an ovalbumin-induced murine model.

BACKGROUND: Growing evidence shows that enhancer of zeste homolog 2 (EZH2) plays a role in various physiological functions and cancer pathogenesis. However, its contribution to allergic diseases remains controversial. We sought to investigate the role of EZH2 in the pathogenesis of allergic airway inflammation. METHODS: 3-Deazaneplanocin A (DZNep), an indirect inhibitor of EZH2, was administered via intraperitoneal injection in an ovalbumin (OVA)-induced murine model of allergic airway inflammation. The expression of EZH2 in the allergic airway tissues was examined by immunohistochemistry (IHC) and western blot. The inflammatory cell infiltration and the goblet cell hyperplasia in the murine nose and lung were detected by hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Levels of cytokines, including IL-4, IFN-γ, IL-6, and IL-10, were evaluated in the bronchoalveolar lavage fluid (BALF) using Enzyme-linked immune sorbent assay (ELISA). RESULTS: EZH2 expression was inhibited by DZNep treatment (P < 0.05). The administration of DZNep significantly inhibited the inflammatory cell infiltration (P < 0.0001) and goblet cell hyperplasia (P < 0.001). Moreover, it suppressed the secretion of IL-4 (P < 0.0001) and IL-6 (P < 0.01) in the BALF. CONCLUSIONS: Our findings demonstrate that DZNep attenuates allergic airway inflammation and could be a new therapeutic option for allergic rhinitis and asthma.

The relationship between malnutrition and TH 2 immune markers: a study in school-aged children of different socio-economic backgrounds in Makassar, Indonesia.

OBJECTIVE: The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TH 2 immune markers in school-aged children in Makassar, Indonesia. METHODS: A cross-sectional study was performed in five schools where socio-demographic characteristics were recorded. Children's standardised z-scores of body mass index (z-BMI) and age-standardised z-scores of height (z-HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin-like growth factor (IGF-1) and TH 2 immune markers were measured. RESULTS: In total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99-4.23) and IGF-1 (GMR 1.45, 95% CI: 1.15-1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49-0.66 and GMR 0.78, 95% CI: 0.63-0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64-0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50-4.78) but no relationship was found with the other TH 2 immune markers. CONCLUSION: Malnutrition is prominent in school-aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.

OBJECTIF: La charge de l'insuffisance pondérale reste un problème majeur en Indonésie et parallèlement, la prévalence du surpoids augmente. La malnutrition est un déterminant majeur de la santé et a été associée à des troubles allergiques chez les enfants. Nous avons examiné la relation entre la malnutrition et les marqueurs immunitaires TH 2 chez les enfants d'âge scolaire à Makassar, en Indonésie. MÉTHODES: Etude transversale dans cinq écoles où les caractéristiques sociodémographiques ont été enregistrées. Les scores z standardisés de l'indice de masse corporelle (z-IMC) et les scores z standardisés pour l'âge de la taille (z-HA) pour les enfants ont été évalués en utilisant les normes de croissance de l'enfant de l'OMS. La réactivité du test cutané (SPT) a été déterminée pour les allergènes d'acariens. L'état de l'infection par les helminthes, les hormones (de croissance), y compris le facteur de croissance analogue à l'insuline (IGF-1) et les marqueurs immunitaires TH 2 ont été mesurés. RÉSULTATS: Au total, 954 enfants ont été inclus, dont 21,6% en insuffisance pondérale et 14,8% en surpoids. Après contrôle des facteurs de confusion, le surpoids était positivement associé à la leptine (GMR 3,55, IC95%: 2,99-4,23) et à l'IGF-1 (GMR 1,45 ; IC95%: 1,15-1,82), tandis que l'insuffisance pondérale était associée négativement (respectivement GMR 0,57 ; IC95%: 0,49-0,66 et GMR 0,78 ; IC95%: 0,63-0,97). L'insuffisance pondérale était associée à un nombre plus faible d'éosinophiles (GMR 0,79 ; IC95%: 0,64-0,97) mais pas aux taux d'IgE totaux ou à la réactivité du SPT. Le surpoids était positivement associé à la réactivité du SPT (OR ajusté 2,68 ; IC95%: 1,50-4,78) mais aucune relation n'a été trouvée avec les autres marqueurs immunitaires T H 2. CONCLUSION: La malnutrition est importante chez les enfants d'âge scolaire à Makassar, avec un surpoids associé à une réactivité accrue du SPT. Par conséquent, les interventions devraient se concentrer sur la dénutrition, mais aussi sur le surpoids pour prévenir l'augmentation des troubles allergiques en Indonésie.

Behind Enemy Lines: Immunomodulatory Armamentarium of the Schistosome Parasite.

The deeply rooted, intricate relationship between the Schistosoma parasite and the human host has enabled the parasite to successfully survive within the host and surreptitiously evade the host's immune attacks. The parasite has developed a variety of strategies in its immunomodulatory armamentarium to promote infection without getting harmed or killed in the battlefield of immune responses. These include the production of immunomodulatory molecules, alteration of membranes, and the promotion of granuloma formation. Schistosomiasis thus serves as a paradigm for understanding the Th2 immune responses seen in various helminthiases. This review therefore aims to summarize the immunomodulatory mechanisms of the schistosome parasites to survive inside the host. Understanding these immunomodulatory strategies not only provides information on parasite-host interactions, but also forms the basis in the development of novel drugs and vaccines against the schistosome infection, as well as various types of autoimmune and inflammatory conditions.

Piperine Ameliorates Trimellitic Anhydride-Induced Atopic Dermatitis-Like Symptoms by Suppressing Th2-Mediated Immune Responses via Inhibition of STAT6 Phosphorylation.

Atopic dermatitis (AD) is a common inflammatory skin disease predominately related to Type 2 helper T (Th2) immune responses. In this study, we investigated whether piperine is able to improve AD symptoms using a trimellitic anhydride (TMA)-induced AD-like mouse model. Topical treatment with piperine reduced ear swelling (ear thickness and epidermal thickness) induced by TMA exposure. Furthermore, piperine inhibited pro-inflammatory cytokines such as TNF-α and IL-1ß in mouse ears, compared with the TMA-induced AD group. In measuring allergic immune responses in draining lymph nodes (dLNs), we found that IL-4 secretion, GATA3 mRNA level, and STAT6 phosphorylation were suppressed by piperine treatment. In an ex vivo study, piperine also inhibited the phosphorylation of STAT6 on the CD4+ T cells isolated from splenocytes of BALB/c mice, and piperine suppressed IL-4-induced CCL26 mRNA expression and STAT6 phosphorylation in human keratinocytes resulting in the inhibition of infiltration of CCR3+ cells into inflammatory lesions. These results demonstrate that piperine could ameliorate AD symptoms through suppression of Th2-mediated immune responses, including the STAT6/GATA3/IL-4 signaling pathway. Therefore, we suggest that piperine is an excellent candidate as an inhibitor of STAT6 and may help to improve AD symptoms.