Fcγ receptors are crucial for the expression of acquired resistance to virulent Salmonella enterica serovar Typhimurium in vivo but are not required for the induction of humoral or T‐cell‐mediated immunity

Abstract

SummaryAntibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcc receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FccRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FccRI, II, III )/) mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FccR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T-and B-cell immunity to the bacterium in vivo.

Contribution of Thy1+NK cells to protective IFN-γ production duringSalmonellaTyphimurium infections

“…Using different vaccination regimens with growth-attenuated mutants of S. Typhimurium, we made several important observations. First, BRD509-afforded protection from WT infection was not as striking as reported by others (37,38). In fact, our data are consistent with a study showing that BRD509 infection provided long-term protection to only ∼50% of mice (23).…”

“…Given the importance of IFN-γ in recall responses against Salmonella (36) and recent reports that Thy1 + NK cells can confer specific immune memory (27), we assessed whether Thy1 + NK cells also contributed to protection against secondary Salmonella infection. Although it is well established that prior infection with growth-attenuated Salmonella strains, such as BRD509, improves subsequent control of otherwise lethal WT S. Typhimurium infections, the degree of such protection is variable (23,(37)(38)(39). Indeed, we observed that only ∼50% of BRD509-infected B6 mice survived secondary infections with WT S. Typhimurium beyond 10 to 20 d (Fig.…”

Influence of Promoter, Gene Copy Number, and Preexisting Immunity on Humoral and Cellular Responses to a Vectored Antigen Delivered by a Salmonella enterica Vaccine

“…The results demonstrated that humoral and T-cell responses were induced from either of two promoters, from either the plasmid or the chromosome, and that preexposure to the empty homologous vector, STM-1, or the heterologous vector, S. enterica serovar Enteritidis, had no detrimental effect on subsequent antigen-specific responses. In the case of homologous preexposure, responses were generally greater, and this was correlated with an increased uptake of Salmonella by macrophages in vitro after opsonization with immune sera.Salmonella enterica strains have been well characterized for the delivery of heterologous vaccine antigens in several animal models (4,5,8, 11, 22,39,43,50). The potential advantages of live attenuated vaccines, such as the simple mode of inoculation and generation of strong immune responses, make them ideal candidates for the delivery of antigens (38-40, 57).…”

Salmonella Virulence Factor SsrAB Regulated Factor Modulates Inflammatory Responses by Enhancing the Activation of NF-κB Signaling Pathway

“…Apoptosis of macrophages in the liver is observed during systemic Salmonella infection (65)(66)(67). This observation raises a hypothesis that apoptotic host cell death might constitute a mechanism allowing bacterial spread to new cells that occurs in the context of a far more active necrotic cell death process, ensuring an ongoing protective intracellular environment in which a subset of bacteria can avoid detection and targeting by the humoral branch of the immune system (68)(69)(70). In cell culture, Salmonella-induced apoptosis requires the activation of TLR4 by bacterial LPS (65,71).…”