Sepsis leads to a reduced antigen‐specific primary antibody response

Abstract

Immunosuppression, impaired cytokine production and high susceptibility to secondary infections are characteristic for septic patients, and for mice after induction of polymicrobial septic peritonitis by sublethal cecal ligation and puncture (CLP). Here, we demonstrate that CLP markedly altered subsequent B-cell responses. Total IgG and IgM levels, as well as the memory B-cell response, were increased in septic mice, but antigenspecific primary antibody production was strongly impaired. We found that two days after CLP, CD11b 1 splenocytes were activated as demonstrated by the increased expression of activation markers, expression of arginase and production of NO by immature myeloid cells. The in vivo clearance of a bacterial infection was not impaired. DCs demonstrated reduced IL-12 production and altered antigen presentation, resulting in decreased proliferation but enhanced IFN-c production by CD4 1 cells. CD4 1 T cells from mice immunized on day 2 after CLP showed reduced Th1 and Th2 cytokine production. In addition, there was an increase in Treg cells. Interestingly, levels of immature B cells decreased but levels of mature B cells increased two days after CLP. However, adoptive transfer of naïve CD4 1 T cells, naïve B cells, or naïve DCs did not rescue the antigen-specific antibody response.

TNFR2 maintains adequate IL-12 production by dendritic cells in inflammatory responses by regulating endogenous TNF levels

“…We have previously shown that total cell, B and T cell numbers in the spleen are reduced 2 d after CLP. 18 Here, we detected a similar reduction of total splenocytes and splenic lymphocyte numbers after CLP in TNFR2-deficient mice. However, CLP hardly affected the cell numbers of CD11b + in TNFR2-deficient mice.…”

Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

“…In contrast, levels of IL-10 are elevated in nonsurvivors relative to survivors (113,359,439). In both experimental models and patients with sepsis, APCs demonstrate decreased capacity to stimulate the T-cell proliferative response compared with healthy controls (113,227,246). These findings indicate that during sepsis there is a marked loss in the immune system's ability to detect microbes and appropriately activate other cells involved in the host response, and that reversal of these abnormalities may contribute to survival.…”

Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis

“…It was found that the percentage of IL-2-secreting T cells was significantly lower when cultured with DC from septic mice as compared with control mice [33]. This finding was also confirmed when OT-II CD4 + T cells were incubated with DCs in the presence of antigen [60]. However, peritoneal DCs and splenic DCs from CLP mice both showed higher capacity to trigger proliferative response of T cells than those from sham group [28].…”