Abstract
In primary infection with Salmonella, it has been reported—without consideration of Salmonella's functions—that humoral immunity plays no role in the clearance of bacteria. In fact, Salmonella targets and suppresses several aspects of humoral immunity, including B cell lymphopoiesis, B cell activation, and IgG production. In particular, the suppression of IgG-secreting plasma cell maintenance allows the persistence of Salmonella in tissues. Therefore, the critical role(s) of humoral immunity in the response to Salmonella infection, especially at the late phase, should be re-investigated. The suppression of IgG plasma cell memory strongly hinders vaccine development against non-typhoidal Salmonella (NTS) because Salmonella can also reduce humoral immune memory against other bacteria and viruses, obtained from previous vaccination or infection. We propose a new vaccine against Salmonella that would not impair humoral immunity, and which could also be used as a treatment for antibody-dependent autoimmune diseases to deplete pathogenic long-lived plasma cells, by utilizing the Salmonella's own suppression mechanism of humoral immunity.
Highlights
The immune system, i.e., innate and adaptive immunity, can overcome many types of bacterial infections
McSorley and Jenkins showed (i) that Salmonella can survive in the tissues of naive wild-type and B cell-deficient mice until day 35 after infection, suggesting that antibodies and B cells are not necessary for the clearance of Salmonella, and (ii) that injection of heat-killed Salmonella induces a provision of anti-Salmonella IgG from day 20, data of antiSalmonella IgG titers in mice infected with live Salmonella are lacking [24]
We have shown that Salmonella inhibits the persistence of IgG-secreting plasma cells in the bone marrow (BM) of mice, which are the main source of serum IgG, by secreting a Salmonella protein known as SiiE [41] (Figure 1)
Summary
The immune system, i.e., innate and adaptive immunity, can overcome many types of bacterial infections. Typhimurium as a model of vaccination resulted in the generation of immune memory against Salmonella and protection against death from challenge with a virulent strain of the bacteria [16, 17]. Susceptible mice can resolve a primary infection with attenuated Salmonella strains which requires a functioning immune system that can develop a T-bet-dependent Th1 cell response and IFNγ production to activate infected macrophages [19, 21].
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