Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.

Boosting the suppressive effects of Ascaris suum components in IFN-γ-deficient mice / Potencialização do efeito supressor de componentes do Ascaris suum em camundongos deficientes em IFN-γ

High molecular weight components from Ascaris suum extract suppress ovalbumin-specific immunity in mice. In IFN-γ-deficient mice, ovalbumin-specific delayed-type hypersensitivity reactions are more strongly downregulated by these suppressive components. Here, the cellularity of the delayed-type hypersensitivity reaction in IFN-γ-deficient mice and the increased downregulation induced by Ascaris suum components were analyzed. IL-12p40-dependent neutrophilic influx was predominant. Suboptimal doses of the suppressive fraction from this nematode completely inhibited the hypersensitivity reaction, thus indicating intensification of the immunosuppression under conditions of intense recruitment of IFN-γ-independent neutrophils.

Componentes de alto peso molecular do extrato de Ascaris suum suprimem a imunidade específica à ovalbumina em camundongos. Em camundongos geneticamente deficientes de IFN-γ a reação de hipersensibilidade tardia específica para ovalbumina foi mais fortemente prejudicada por estes componentes supressivos. Aqui, a celularidade da reação de hipersensibilidade tardia em camundongos deficientes de IFN-γ e o incremento na supressão induzida por componentes do Ascaris suum foram analisados. Influxo neutrofílico, dependente de IL-12p40, foi predominante. Dose sub-ótima da fração supressiva do nematódeo inibiu completamente a reação de hipersensibilidade, indicando uma intensificação da imunossupressão em condições de recrutamento intenso de neutrófilos independente de IFN-γ.

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d) developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.

Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos inatos no controle da infecção. Por outro lado, o haplótipo do MHC não influenciou na resistência/susceptibilidade, na medida em que linhagens de camundongos com um mesmo "background'' genético, mas diferentes haplótipos de MHC (H2b e H2d) apresentam o índice de mortalidade e número de cistos semelhantes após a infecção com aquelas cepas do parasita. Em contraste, o "background'' genético de C57BL/6, mas não o haplótipo de MHC, foi crítico para o desenvolvimento de inflamação intestinal causada pelas cepas estudadas. Finalmente, com relação aos mecanismos efetores, observamos que linfócitos B e T CD8+ controlam a sobrevivência após infecção. Por outro lado, a ativação da enzima óxido nítrico sintase induzida foi um fator importante para controle do número de cistos cerebrais em camundongos infectados com cepas do Tipo I/III. Esses achados são relevantes para o melhor entendimento dos mecanismos imunológicos envolvidos na proteção e patogênese durante infecção com T. gondii.

Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice

The critical role of interferon-gamma (IFN-g) in the resistance of C57Bl/6 mice to Leishmania major is widely established but its role in the relative resistance of these animals to L. amazonensis infection is still not clear. In this work we use C57Bl/6 mice congenitally deficient in the IFN-g gene (IFN-g KO) to address this issue. We found that IFN-g KO mice were as resistant as their wild-type (WT) counterparts at least during the first two months of infection. Afterwards, whereas WT mice maintained lesion growth under control, IFN-g KO mice developed devastating lesions. At day 97 of infection, their lesions were 9-fold larger than WT controls, concomitant with an increased parasite burden. At this stage, lesion-draining cells from IFN-g KO mice had impaired capacity to produce interleukin-12 (IL-12) and tumour necrosis factor-a in response to parasite antigens whereas IL-4 was slightly increased in comparison to infected WT mice. Together, these results show that IFN-g is not critical for the initial control of L. amazonensis infection in C57Bl/6 mice, but is essencial for the developmente of a protective Th1 type immune response in the later stages.

Concentraciones séricas de interferón - gamma en embarazadas normales / Serum concentration of interferon -gamma in normal pregnancy

Estudiar los niveles séricos de interferon-gamma durante el embarazo. Estudio prospectivo de 90 embarazadas, 30 por cada trimestre y un control de 30 mujeres normales no gestantes. La cuantificación de la citocina en suero se hizo siguiendo la técnica de inmunoanálisis enzimático de doble anticuerpo. Cátedra de Inmunología. Facultad de Medicina. Universidad del Zulia. Hubo disminución significativa y progresiva de los valores de la citocina, con diferencia válida respecto a los controles (p<0,001). Durante todo el embarazo hay una caida de los valores séricos del interferón-Gamma, lo que facilitaría la invación trofoblástica y la inhibición de la actividad de las células asesinas naturales, pero produce un estado de suceptibilidad a patógenos intracelulares

Síndrome de hiper IgE: revisión bibliográfica / Hyper IgE syndrome: bibliography review

El síndrome de hiper IgE (SHIE) es una rara entidad que se caracteriza por presentar infecciones cutáneas y respiratorias, sobre todo neumonías a estafilococo, con posterior formación de neumatoceles, disturbios en el metabolismo óseo y una IgE sumamente elevada. En el presente artículo se trata de actualizar el tema en sus aspectos fisiopatológicos, inmunológicos y nuevas conductas de tratamiento