RESUMO
Gastrointestinal mucosa reserves abundant Th17 cells where host response to commensal bacteria maintains Th17-cell generation. Although functional heterogeneity and dynamic plasticity of Th17 cells appear to be involved in chronic inflammatory disorders, how their plasticity is regulated in intestinal mucosa is unknown. Here we show that innate TRIF signaling regulates intestinal Th17-cell generation and plasticity during colitis. Absence of TRIF in mice resulted in increased severity of experimental colitis, which was associated with aberrant generation of Th17 cells especially of interferon (IFN)-γ-expressing Th17 cells in the lamina propria. The abnormal generation and plasticity of Th17 cells involved impaired expression of interleukin (IL)-27p28 by lamina propria macrophages but not dendritic cells. Treatment of TRIF-deficient mice with IL-27p28 during colitis reduced the number and IFN-γ expression of Th17 cells in the intestine. In vitro, TRIF-deficient macrophages induced more Th17 cells than wild-type (WT) macrophages during co-culture with WT naive T cells in response to cecal bacterial antigen. Many of Th17 cells induced by TRIF-deficient macrophages expressed IFN-γ due to impaired expression of IL-27p28 by macrophages and defective activation of STAT1 in T cells. These results outline TRIF-dependent regulatory mechanism by which host response to intestinal bacteria maintains Th17-cell-mediated pathology during colitis.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Colite/genética , Colite/imunologia , Células Th17/imunologia , Células Th17/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Diferenciação Celular , Colite/metabolismo , Colite/patologia , Modelos Animais de Doenças , Expressão Gênica , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-27/genética , Interleucina-27/metabolismo , Interleucina-27/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Fator de Transcrição STAT1/metabolismo , Índice de Gravidade de Doença , Células Th17/citologia , Células Th17/efeitos dos fármacosRESUMO
Serotype G9 may be the fifth most common human rotavirus serotype, after serotypes G1 to G4. In three cross-sectional studies of childhood diarrhea, we have detected serotype G9 rotaviruses for the first time in Libya, Kenya, and Cuba. Serotype G9 constituted 27% of all rotaviruses identified, emphasizing the reemergence of serotype G9 and suggesting that future human rotavirus vaccines will need to protect against disease caused by this serotype.
Assuntos
Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Cuba/epidemiologia , Fezes/virologia , Humanos , Lactente , Quênia/epidemiologia , Líbia/epidemiologia , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/genética , SorotipagemRESUMO
During the 1981 epidemic of dengue type 2 in Cuba a study was done of 124 children from 0 to 14 years of age who had dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), degress III and IV. Almost all these children (98 percent) had neutralizing antibodies against the dengue type 1 and 2 viruses, indicating that they had already been previously infected with the type 1 virus. Neither sex was predominant among the patients. The frequency of the serious form of the disease was significantly greater among white children (p0.01) than among black or mulatto. Subjects between the ages of 4 and 11 were most apt to suffer serious clinical manifestations of the disease. In most of the cases the shock occurred four or five days after the appearance of the signs and symptoms, often preceded by abdominal pain. The most frequent clinical manifestations were fever, vomiting, and hepatomegaly. In 68.5 percent of the children there were hemorrhagic manifestations, mainly petechia and hematemesis. It was noted that and unusually high percentage of the children in the study had a personal or family background of asthma. In general, the results confirm that infection with the dengue type 1 virus shortly before infection with the type 2 virus is closely related to the appearance of DHF/DSS. In addition, the high percentage of children with a background of asthma supports the theory that this and other forms