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Semaphorin 3E Protects against Chlamydial Infection by Modulating Dendritic Cell Functions.
Thomas, Rony; Wang, Shuhe; Shekhar, Sudhanshu; Peng, Ying; Qiao, Sai; Zhang, Chunyan; Shan, Lianyu; Movassagh, Hesam; Gounni, Abdelilah S; Yang, Jie; Yang, Xi.
Afiliación
  • Thomas R; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Wang S; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Shekhar S; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Peng Y; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Qiao S; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Zhang C; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Shan L; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Movassagh H; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Gounni AS; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Yang J; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
  • Yang X; Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada x.yang@umanitoba.ca.
J Immunol ; 206(6): 1251-1265, 2021 03 15.
Article en En | MEDLINE | ID: mdl-33504621
Recent studies have identified semaphorin 3E (Sema3E) as a novel mediator of immune responses. However, its function in immunity to infection has yet to be investigated. Using a mouse model of chlamydial lung infection, we show that Sema3E plays a significant role in the host immune response to the infection. We found that Sema3E is induced in the lung after chlamydial infection, and Sema3E deficiency has a detrimental impact on disease course, dendritic cell (DC) function, and T cell responses. Specifically, we found that Sema3E knockout (KO) mice exhibited higher bacterial burden, severe body weight loss, and pathological changes after Chlamydia muridarum lung infection compared with wild-type (WT) mice. The severity of disease in Sema3E KO mice was correlated with reduced Th1/Th17 cytokine responses, increased Th2 response, altered Ab response, and a higher number of regulatory CD4 T cells. Moreover, DCs isolated from Sema3E KO mice showed lower surface expression of costimulatory molecules and production of IL-12, but higher expression of PD-L1, PD-L2, and IL-10 production. Functional DC-T cell coculture studies revealed that DCs from infected Sema3E KO mice failed to induce Th1 and Th17 cell responses compared with DCs from infected WT mice. Upon adoptive transfer, mice receiving DCs from Sema3E KO mice, unlike those receiving DCs from WT mice, were not protected against challenge infection. In conclusion, our data evidenced that Sema3E acts as a critical factor for protective immunity against intracellular bacterial infection by modulating DC functions and T cell subsets.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Linfocitos T CD4-Positivos / Infecciones por Chlamydia / Subgrupos de Linfocitos T / Semaforinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Linfocitos T CD4-Positivos / Infecciones por Chlamydia / Subgrupos de Linfocitos T / Semaforinas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos