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1.
Cell Rep ; 37(2): 109816, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644571

RESUMO

Cytokines are typically single gene products, except for the heterodimeric interleukin (IL)-12 family. The two subunits (IL-12p40 and IL-12p35) of the prototype IL-12 are known to be simultaneously co-expressed in activated myeloid cells, which secrete the fully active heterodimer to promote interferon (IFN)γ production in innate and adaptive cells. We find that chimeric mice containing mixtures of cells that can only express either IL-12p40 or IL-12p35, but not both together, generate functional IL-12. This alternate two-cell pathway requires IL-12p40 from hematopoietic cells to extracellularly associate with IL-12p35 from radiation-resistant cells. The two-cell mechanism is sufficient to propel local T cell differentiation in sites distal to the initial infection and helps control systemic dissemination of a pathogen, although not parasite burden, at the site of infection. Broadly, this suggests that early secretion of IL-12p40 monomers by sentinel cells at the infection site may help prepare distal host tissues for potential pathogen arrival.


Assuntos
Células Dendríticas/metabolismo , Subunidade p35 da Interleucina-12/metabolismo , Subunidade p40 da Interleucina-12/metabolismo , Leishmania major/patogenicidade , Leishmaniose Cutânea/metabolismo , Células Estromais/metabolismo , Linfócitos T/metabolismo , Animais , Comunicação Celular , Células Dendríticas/imunologia , Células Dendríticas/parasitologia , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita , Interferon gama/metabolismo , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Leishmania major/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Multimerização Proteica , Transdução de Sinais , Células Estromais/imunologia , Células Estromais/parasitologia , Linfócitos T/imunologia , Linfócitos T/parasitologia
2.
Front Immunol ; 9: 2794, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619242

RESUMO

After infection with Trypanosoma cruzi, the etiologic agent of Chagas disease, immunosuppression, and apoptosis of mature lymphocytes contribute to the establishment of the parasite in the host and thereby to persistence and pathology in the chronic stage of infection. In a systemic mouse model of experimental Chagas disease, we have demonstrated a strong depletion of mature B cells in the spleen during the first 2 weeks of infection. Remarkably, the decrease in this cell population commenced already in the bone marrow from infected mice and was a concomitant of an increased apoptosis in pro- and pre-B cell populations. Pro- and pre-B cells in the bone marrow showed a significant reduction accompanied by a functional disturbance of bone marrow-derived stromal cells resulting in diminished levels of IL-7, an essential factor for the development of B cell precursors. Ex vivo, stromal cells isolated from the bone marrow of infected mice had a strikingly impaired capacity to maintain the development of pro- and pre-B cells obtained from uninfected animals. Together, the reduction of an active humoral immune response during acute Chagas disease suggests to be an initial immune evasion mechanism of the parasite to establish persistent infection. Therefore, prevention of B cell depletion by rescuing the stromal cells during this early phase, could give rise to new therapeutic approaches.


Assuntos
Células da Medula Óssea/imunologia , Doença de Chagas/imunologia , Tolerância Imunológica , Trypanosoma cruzi/imunologia , Doença Aguda , Animais , Apoptose/imunologia , Células da Medula Óssea/parasitologia , Células da Medula Óssea/patologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Doença Crônica , Interleucina-7/imunologia , Camundongos , Células Precursoras de Linfócitos B/imunologia , Células Precursoras de Linfócitos B/parasitologia , Células Precursoras de Linfócitos B/patologia , Baço/imunologia , Baço/parasitologia , Baço/patologia , Células Estromais/imunologia , Células Estromais/parasitologia , Células Estromais/patologia
3.
Cell Immunol ; 308: 13-18, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27444131

RESUMO

Gender-associated differences in the outcome of infections are well known. Apart from behavior-released differences in their incidence, immunological factors also contribute to disease outcome. The underlying mechanisms are often unknown. Here, we show that in murine experimental leishmaniasis, female mice develop larger skin lesions that harbor significantly more parasites, exhibit increased parasite dissemination to visceral organs associated with a shift towards T helper (Th) 2 immunity with increased levels of IL-4. Antigen presenting cells (APC) responsible for T cell priming, such as macrophages or dendritic cells, were not involved in the process. Additionally, in adoptive transfer experiments, we show that differences in the lymphoid lineage are also not critical for mediating these gender-dependent effects. In summary, neither myeloid nor lymphoid cells contribute to disease outcome against this important human pathogen, but stromal cells influenced by e.g. hormonal effects in addition to other parts of the immune system might play a role.


Assuntos
Hormônios/metabolismo , Leishmaniose Cutânea/imunologia , Sexo , Células Estromais/imunologia , Células Th2/imunologia , Animais , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Humanos , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/imunologia , Células Mieloides/parasitologia , Células Estromais/parasitologia , Equilíbrio Th1-Th2 , Células Th2/parasitologia
4.
Parasite Immunol ; 38(4): 218-27, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26832322

RESUMO

While Trichomonas vaginalis, a cause of sexually transmitted infection, is known as a surface-dwelling protozoa, trichomonads have been detected in prostatic tissue from benign prostatic hyperplasia and prostatitis by immunoperoxidase assay or PCR. However, the immune response of prostate stromal cells infected with T. vaginalis has not been investigated. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate stromal cells. Incubation of a human prostate stromal myofibroblast cells (WPMY-1) with live T. vaginalis T016 increased expression of the inflammatory chemokines CXCL8 and CCL2. In addition, TLR4, ROS, MAPK and NF-κB expression increased, while inhibitors of TLR4, ROS, MAPKs and NF-κB reduced CXCL8 and CCL2 production. Medium conditioned by incubation of WPMY-1 cells with T. vaginalis stimulated the migration of human neutrophils and monocytes (THP-1 cells). We conclude that T. vaginalis increases CXCL8 and CCL2 production by human prostate stromal cells by activating TLR4, ROS, MAPKs and NF-κB, and this in turn attracts neutrophils and monocytes and leads to an inflammatory response. This study is the first attempt to demonstrate an inflammatory reaction in prostate stromal cells caused by T. vaginalis.


Assuntos
Próstata/patologia , Trichomonas vaginalis/imunologia , Linhagem Celular , Movimento Celular , Quimiocina CCL2/biossíntese , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-8/biossíntese , Masculino , Miofibroblastos/imunologia , Miofibroblastos/metabolismo , Miofibroblastos/parasitologia , NF-kappa B/metabolismo , Neutrófilos/fisiologia , Próstata/imunologia , Próstata/parasitologia , Espécies Reativas de Oxigênio/metabolismo , Células Estromais/metabolismo , Células Estromais/parasitologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Tricomoníase/imunologia , Tricomoníase/parasitologia
5.
Parasite ; 21: 38, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25083732

RESUMO

Cellular culture infection with Trypanosoma cruzi is a tool used to dissect the biological mechanisms behind Chagas disease as well as to screen potential trypanocidal compounds. Data on these models are highly heterogeneous, which represents a challenge when attempting to compare different studies. The purpose of this review is to provide an overview of the cell culture infectivity assays performed to date. Scientific journal databases were searched for articles in which cultured cells were infected with any Trypanosoma cruzi strain or isolate regardless of the study's goal. From these articles the cell type, parasite genotype, culture conditions and infectivity results were extracted. This review represents an initial step toward the unification of infectivity model data. Important differences were detected when comparing the pathophysiology of Chagas disease with the experimental conditions used in the analyzed studies. While Trypanosoma cruzi preferentially infects stromal cells in vivo, most of the assays employ epithelial cell lines. Furthermore, the most commonly used parasite strain (Tulahuen-TcVI) is associated with chagasic cardiomyopathy only in the Southern Cone of South America. Suggestions to overcome these discrepancies include the use of stromal cell lines and parasite genotypes associated with the known characteristics of the natural history of Chagas disease.


Assuntos
Células Cultivadas/parasitologia , Doença de Chagas/parasitologia , Parasitologia/métodos , Trypanosoma cruzi/crescimento & desenvolvimento , Animais , Bovinos , Técnicas de Cultura de Células , Cardiomiopatia Chagásica/parasitologia , Células Epiteliais/parasitologia , Genótipo , Haplorrinos , Humanos , Rim/citologia , Mamíferos , Células Estromais/parasitologia , Trypanosoma cruzi/genética , Trypanosoma cruzi/patogenicidade
6.
J Immunol ; 189(9): 4371-8, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23024277

RESUMO

CD4(+) Th2 cytokine responses promote the development of allergic inflammation and are critical for immunity to parasitic helminth infection. Recent studies highlighted that basophils can promote Th2 cytokine-mediated inflammation and that phenotypic and functional heterogeneity exists between classical IL-3-elicited basophils and thymic stromal lymphopoietin (TSLP)-elicited basophils. However, whether distinct basophil populations develop after helminth infection and their relative contributions to anti-helminth immune responses remain to be defined. After Trichinella spiralis infection of mice, we show that basophil responses are rapidly induced in multiple tissue compartments, including intestinal-draining lymph nodes. Trichinella-induced basophil responses were IL-3-IL-3R independent but critically dependent on TSLP-TSLPR interactions. Selective depletion of basophils after Trichinella infection impaired infection-induced CD4(+) Th2 cytokine responses, suggesting that TSLP-dependent basophils augment Th2 cytokine responses after helminth infection. The identification and functional classification of TSLP-dependent basophils in a helminth infection model, coupled with their recently described role in promoting atopic dermatitis, suggests that these cells may be a critical population in promoting Th2 cytokine-associated inflammation in a variety of inflammatory or infectious settings. Collectively, these data suggest that the TSLP-basophil pathway may represent a new target in the design of therapeutic intervention strategies to promote or limit Th2 cytokine-dependent immunity and inflammation.


Assuntos
Basófilos/imunologia , Citocinas/biossíntese , Mucosa Intestinal/imunologia , Células Th2/imunologia , Timo/imunologia , Trichinella spiralis/imunologia , Triquinelose/imunologia , Animais , Basófilos/parasitologia , Basófilos/patologia , Citocinas/fisiologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/parasitologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Células Estromais/imunologia , Células Estromais/parasitologia , Células Estromais/patologia , Células Th2/parasitologia , Células Th2/patologia , Timo/parasitologia , Timo/patologia , Triquinelose/metabolismo , Triquinelose/patologia , Linfopoietina do Estroma do Timo
7.
J Leukoc Biol ; 92(1): 123-31, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22493080

RESUMO

Inflammation alters hematopoiesis, often by decreasing erythropoiesis and enhancing myeloid output. The mechanisms behind these changes and how the BM stroma contributes to this process are active areas of research. In this study, we examine these questions in the setting of murine Toxoplasma gondii infection. Our data reveal that infection alters early myeloerythroid differentiation, blocking erythroid development beyond the Pre MegE stage, while expanding the GMP population. IL-6 was found to be a critical mediator of these differences, independent of hepcidin-induced iron restriction. Comparing the BM with the spleen showed that the hematopoietic response was driven by the local microenvironment, and BM chimeras demonstrated that radioresistant cells were the relevant source of IL-6 in vivo. Finally, direct ex vivo sorting revealed that VCAM(+)CD146(lo) BM stromal fibroblasts significantly increase IL-6 secretion after infection. These data suggest that BMSCs regulate the hematopoietic changes during inflammation via IL-6.


Assuntos
Células Precursoras Eritroides/efeitos dos fármacos , Interleucina-6/farmacologia , Células Progenitoras Mieloides/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Toxoplasma/efeitos dos fármacos , Toxoplasmose/tratamento farmacológico , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/parasitologia , Medula Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Células Precursoras Eritroides/parasitologia , Células Precursoras Eritroides/patologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/parasitologia , Hematopoese/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/parasitologia , Células-Tronco Hematopoéticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Progenitoras Mieloides/parasitologia , Células Progenitoras Mieloides/patologia , Células Estromais/parasitologia , Células Estromais/patologia , Toxoplasma/patogenicidade , Toxoplasmose/parasitologia , Toxoplasmose/patologia
8.
J Immunol ; 185(4): 2360-71, 2010 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-20624948

RESUMO

In the immune system, stromal cells provide specialized niches that control hematopoiesis by coordinating the production of chemokines, adhesion molecules, and growth factors. Stromal cells also have anti-inflammatory effects, including support for the differentiation of hematopoietic progenitors into dendritic cells (DCs) with immune regulatory properties. Together, these observations suggest that the alterations in hematopoiesis commonly seen in infectious disease models, such as experimental visceral leishmaniasis in mice, might result from altered stromal cell function. We report in this study that the stromal cell-derived chemokines CXCL12 and CCL8 cooperate to attract hematopoietic progenitors with the potential to differentiate into regulatory DCs. We also show that infection of murine bone marrow stromal cells by Leishmania donovani enhanced their capacity to support the development of regulatory DCs, as well as their capacity to produce CCL8. Likewise, in experimental visceral leishmaniasis, CCL8 production was induced in splenic stromal cells, leading to an enhanced capacity to attract hematopoietic progenitor cells. Thus, intracellular parasitism of stromal cells modifies their capacity to recruit and support hematopoietic progenitor differentiation into regulatory DCs, and aberrant expression of CCL8 by diseased stromal tissue may be involved in the switch from resolving to persistent infection.


Assuntos
Quimiocina CCL8/metabolismo , Quimiocina CXCL12/metabolismo , Células Dendríticas/metabolismo , Células Estromais/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Quimiocina CCL8/genética , Quimiocina CXCL12/genética , Análise por Conglomerados , Técnicas de Cocultura , Cricetinae , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Perfilação da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Interações Hospedeiro-Patógeno , Leishmania donovani/fisiologia , Leishmaniose Visceral/genética , Leishmaniose Visceral/metabolismo , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/parasitologia
9.
Infect Immun ; 72(10): 5687-92, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15385467

RESUMO

Endosymbiotic Wolbachia bacteria are abundant in the filarial nematodes that cause onchocerciasis (river blindness), including the larvae (microfilariae) that migrate into the cornea. Using a mouse model of ocular onchocerciasis, we recently demonstrated that it is these endosymbiotic bacteria rather than the nematodes per se that induce neutrophil infiltration to the corneal stroma and loss of corneal clarity (Saint Andre et al., Science 295:1892-1895, 2002). To better understand the role of Wolbachia organisms in the pathogenesis of this disease, we examined the fate of these bacteria in the cornea by immunoelectron microscopy. Microfilariae harboring Wolbachia organisms were injected into mouse corneas, and bacteria were detected with antibody to Wolbachia surface protein. Within 18 h of injection, neutrophils completely surrounded the nematodes and were in close proximity to Wolbachia organisms. Wolbachia surface protein labeling was also prominent in neutrophil phagosomes, indicating neutrophil ingestion of Wolbachia organisms. Furthermore, the presence of numerous electron-dense granules around the phagosomes indicated that neutrophils were activated. To determine if Wolbachia organisms directly activate neutrophils, peritoneal neutrophils were incubated with either parasite extracts containing Wolbachia organisms, parasite extracts depleted of Wolbachia organisms (by antibiotic treatment of worms), or Wolbachia organisms isolated from filarial nematodes. After 18 h of incubation, we found that isolated Wolbachia organisms stimulated production of tumor necrosis factor alpha and CXC chemokines macrophage inflammatory protein 2 and KC by neutrophils in a dose-dependent manner. Similarly, these cytokines were induced by filarial extracts containing Wolbachia organisms but not by Wolbachia-depleted extracts. Taken together, these findings indicate that neutrophil activation is an important mechanism by which Wolbachia organisms contribute to the pathogenesis of ocular onchocerciasis.


Assuntos
Modelos Animais de Doenças , Filarioidea/microbiologia , Ativação de Neutrófilo , Neutrófilos/imunologia , Neutrófilos/microbiologia , Oncocercose Ocular/imunologia , Wolbachia/imunologia , Animais , Extratos Celulares , Quimiocinas/biossíntese , Quimiocinas/imunologia , Córnea/imunologia , Córnea/microbiologia , Córnea/parasitologia , Córnea/patologia , Citocinas/biossíntese , Citocinas/imunologia , Filarioidea/fisiologia , Camundongos , Neutrófilos/citologia , Oncocercose Ocular/microbiologia , Oncocercose Ocular/parasitologia , Oncocercose Ocular/patologia , Fagocitose , Células Estromais/imunologia , Células Estromais/microbiologia , Células Estromais/parasitologia , Vacúolos/microbiologia , Wolbachia/isolamento & purificação
10.
J Immunol ; 166(6): 4035-41, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11238651

RESUMO

Infiltration of neutrophils and eosinophils into the mammalian cornea can result in loss of corneal clarity and severe visual impairment. To identify mediators of granulocyte recruitment to the corneal stroma, we determined the relative contribution of chemokine receptors CXC chemokine receptor (CXCR)-2 (IL-8R homologue) and CCR1 using a murine model of ocular onchocerciasis (river blindness) in which neutrophils and eosinophils migrate from peripheral vessels to the central cornea. CXCR2(-/-) and CCR1(-/-) mice were immunized s.c. and injected into the corneal stroma with Ags from the parasitic helminth Onchocerca volvulus. We found that production of macrophage-inflammatory protein (MIP)-2, KC, and MIP-1 alpha was localized to the corneal stroma, rather than to the epithelium, which was consistent with the location of neutrophils in the cornea. CCR1 deficiency did not inhibit neutrophil or eosinophil infiltration to the cornea or development of corneal opacification. In marked contrast, neutrophil recruitment to the corneas of CXCR2(-/-) mice was significantly impaired (p < 0.0001 compared with control, BALB/c mice) with only occasional neutrophils detected in the central cornea. Furthermore, CXCR2(-/-) mice developed only mild corneal opacification compared with BALB/c mice. These differences were not due to impaired KC and MIP-2 production in the corneal stroma of CXCR2(-/-) mice, which was similar to BALB/c mice. Furthermore, although MIP-1 alpha production was lower in CXCR2(-/-) mice than BALB/c mice, eosinophil recruitment to the cornea was not impaired. These observations demonstrate the critical role for CXCR2 expression in neutrophil infiltration to the cornea and may indicate a target for immune intervention in neutrophil-mediated corneal inflammation.


Assuntos
Quimiocinas CC/metabolismo , Córnea/imunologia , Ceratite/imunologia , Infiltração de Neutrófilos/imunologia , Onchocerca volvulus/imunologia , Oncocercose Ocular/imunologia , Receptores de Quimiocinas/biossíntese , Receptores de Interleucina-8B/biossíntese , Animais , Anticorpos Anti-Helmínticos/biossíntese , Movimento Celular/genética , Movimento Celular/imunologia , Quimiocina CCL4 , Quimiocina CXCL1 , Quimiocina CXCL2 , Quimiocinas/biossíntese , Quimiocinas CC/biossíntese , Quimiocinas CXC , Córnea/metabolismo , Córnea/parasitologia , Córnea/patologia , Opacidade da Córnea/genética , Opacidade da Córnea/imunologia , Opacidade da Córnea/parasitologia , Citocinas/biossíntese , Eosinófilos/imunologia , Eosinófilos/metabolismo , Epitélio Corneano/imunologia , Epitélio Corneano/metabolismo , Epitélio Corneano/parasitologia , Imunoglobulina G/biossíntese , Ceratite/genética , Ceratite/parasitologia , Ceratite/patologia , Proteínas Inflamatórias de Macrófagos/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oncocercose Ocular/genética , Oncocercose Ocular/patologia , Receptores CCR1 , Receptores de Quimiocinas/deficiência , Receptores de Quimiocinas/genética , Receptores de Interleucina-8B/deficiência , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/fisiologia , Células Estromais/imunologia , Células Estromais/metabolismo , Células Estromais/parasitologia
11.
Infect Immun ; 68(6): 3455-62, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10816498

RESUMO

With the aim of developing an appropriate in vitro model of the sequestration of developing Plasmodium falciparum sexual-stage parasites, we have investigated the cytoadherence of gametocytes to human bone marrow cells of stromal and endothelial origin. Developing stage III and IV gametocytes, but not mature stage V gametocytes, adhere to bone marrow cells in significantly higher densities than do asexual-stage parasites, although these adhesion densities are severalfold lower than those encountered in classical CD36-dependent assays of P. falciparum cytoadherence. This implies that developing gametocytes undergo a transition from high-avidity, CD36-mediated adhesion during stages I and II to a lower-avidity adhesion during stages III and IV. We show that this adhesion is CD36 independent, fixation sensitive, stimulated by tumor necrosis factor alpha, and dependent on divalent cations and serum components. These data suggest that gametocytes and asexual parasites utilize distinct sets of receptors for adhesion during development in their respective sequestered niches. To identify receptors for gametocyte-specific adhesion of infected erythrocytes to bone marrow cells, we tested a large panel of antibodies for the ability to inhibit cytoadherence. Our results implicate ICAM-1, CD49c, CD166, and CD164 as candidate bone marrow cell receptors for gametocyte adhesion.


Assuntos
Células da Medula Óssea/parasitologia , Adesão Celular , Eritrócitos/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Receptores de Superfície Celular/isolamento & purificação , Animais , Endotélio Vascular/parasitologia , Humanos , Reprodução , Células Estromais/parasitologia
12.
Blood ; 95(5): 1642-51, 2000 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10688819

RESUMO

Alterations in hematopoiesis are common in experimental infectious disease. However, few studies have addressed the mechanisms underlying changes in hematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. In experimental visceral leishmaniasis, caused by infection with the protozoan parasite Leishmania donovani, parasites persist in the spleen and bone marrow, and their expansion in these sites is associated with increases in local hematopoietic activity. The results of this study show that L donovani targets bone marrow stromal macrophages in vivo and can infect and multiply in stromal cell lines of macrophage, but not other lineages in vitro. Infection of stromal macrophages increases their capacity to support myelopoiesis in vitro, an effect mediated mainly through the induction of granulocyte macrophage-colony stimulating factor and tumor necrosis factor-alpha. These data are the first to directly demonstrate that intracellular parasitism of a stromal cell population may modify its capacity to regulate hematopoiesis during infectious disease. (Blood. 2000;95:1642-1651)


Assuntos
Células da Medula Óssea/parasitologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Hematopoese , Leishmania donovani/fisiologia , Leishmaniose Visceral/fisiopatologia , Macrófagos/parasitologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Células da Medula Óssea/metabolismo , Linhagem Celular , Técnicas de Cocultura , Ensaio de Unidades Formadoras de Colônias , Feminino , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Leishmaniose Visceral/parasitologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/metabolismo , Baço/parasitologia , Baço/patologia , Células Estromais/metabolismo , Células Estromais/parasitologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética
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