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B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.

ABSTRACT: Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T-cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined mainly to the FRT and the draining iliac lymph node. Here, we show that rectal infection with LCMV triggers type I/III interferon responses, followed by innate immune activation and lymphocyte recruitment to the colon. In contrast to vaginal exposure, innate immunity controls LCMV replication in the colon, but virus rapidly disseminates systemically. Virus-induced inflammation promotes the recruitment of LCMV target cells to the colon followed by splenic viral dissemination by infected B cells, and to a lesser extent by CD8 T cells. These findings demonstrate major immunological differences between vaginal and rectal exposure to the same viral pathogen, highlighting unique risks associated with each of these common routes of sexual viral transmission.

SUBMITTER: Trapecar M

PROVIDER: S-EPMC6030459 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.

Trapecar Martin M Khan Shahzada S Cohn Benjamin L BL Wu Frank F Sanjabi Shomyseh S

Mucosal immunology 20180219 4

Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T-cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined ma ...[more]

PMID: 29456247

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Project description:Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a receptor for Candida albicans. It is crucial for the immune response of intestinal epithelial cells to this opportunistic pathogen. Moreover, CEACAM1 is of importance for the mucosal colonization by different bacterial pathogens. We therefore studied the influence of the human CEACAM1 receptor in human CEACAM1-transgenic mice on the C. albicans colonization and infection utilizing a colonization/dissemination and a systemic infection mouse model. Our results showed no alterations in the host response between the transgenic mice and the wild-type littermates to the C. albicans infections. Both mouse strains showed comparable C. albicans colonization and mycobiota, similar fungal burdens in various organs, and a similar survival in the systemic infection model. Interestingly, some of the mice treated with anti-bacterial antibiotics (to prepare them for C. albicans colonization via oral infection) also showed a strong reduction in endogenous fungi instead of the normally observed increase in fungal numbers. This was independent of the expression of human CEACAM1. In the systemic infection model, the human CEACAM1 expression was differentially regulated in the kidneys and livers of Candida-infected transgenic mice. Notably, in the kidneys, a total loss of the largest human CEACAM1 isoform was observed. However, the overwhelming immune response induced in the systemic infection model likely covered any CEACAM1-specific effects in the transgenic animals. In vitro studies using bone marrow-derived neutrophils from both mouse strains also revealed no differences in their reaction to C. albicans. In conclusion, in contrast to bacterial pathogens interacting with CEACAM1 on different mucosal surfaces, the human CEACAM1-transgenic mice did not reveal a role of human CEACAM1 in the in vivo candidiasis models used here. Further studies and different approaches will be needed to reveal a putative role of CEACAM1 in the host response to C. albicans.

Dataset Information

B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.

Publications

B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.

Similar Datasets

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