Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause progressive infections in athymic (nu/nu) BALB/c mice

Abstract

Athymic (nu/nu) BALB/c mice and their euthymic (nu/؉) littermates were inoculated intravenously with live attenuated vaccine strains of Salmonella typhimurium. All strains caused progressive infections in the athymic mice but not in their euthymic littermates. Athymic mice given strain SL3261, an aroA derivative of SL1344, in doses between log 4.7 and 5.7 CFU were all severely ill and were killed by weeks 4 to 5. Athymic mice given log 4.7 CFU of a derivative of S. typhimurium C5 carrying a mutation in htrA, encoding a stress protein, were ill and were killed by week 7 in one experiment but survived to week 13 in another. Athymic mice given log 4.6 CFU of a C5 aroD htrA double mutant were ill and were killed at week 7. Athymic mice given SL3261 had high bacterial counts in the reticuloendothelial system at 4 weeks. Athymic mice given SL3261 or C5 htrA made immunoglobulin G3 (IgG3) (and to a lesser extent IgM) antibody to lipopolysaccharide (LPS), whereas euthymic mice made IgM, IgG1, IgG2a, IgG2b, and IgG3 anti-LPS antibodies. The results indicate that both aroA and htrA strains will produce slow, progressively lethal infections in athymic mice, that the htrA strain is more attenuated than the aroA strain as measured by time to death in this model, and that IgG3 anti-LPS antibody alone cannot suppress the progress of infections by very attenuated strains in athymic mice.

Effect of immune serum and role of individual Fcγ receptors on the intracellular distribution and survival of Salmonella enterica serovar Typhimurium in murine macrophages

“…FccRI is a high-affinity receptor for IgG2a and previous work indicates that immunization with live S. enterica serovar Typhimurium leads to production of antibody responses with a high IgG2a content, probably as a result of the simultaneous induction of high levels of IFN-c by Salmonella-specific T helper 1-type T cells. 27,44 In the absence of FccRI, internalization of S. enterica serovar Typhimurium is abrogated and other Fcc receptors (e.g. FccRIII) are unable to compensate for the FccRI deficiency.…”

“…The profile of anti-Salmonella immunoglobulins in the IS was similar to that previously reported. 27,44 The serum contained detectable levels of IgG2a, IgG2b, IgG1 and IgG3 subclasses, as well as immunoglobulin M (IgM) and immunoglobulin A (IgA), as measured by enzyme-linked immunosorbent assay (ELISA) (data not shown). Normal mouse serum (NMS), from non-immunized C57BL/6 mice, was used as a control.…”

miR‐155: an ancient regulator of the immune system

“…When miR-155-deficient mice were treated with attenuated Salmonella, they were able to clear the infection, although antigen-specific antibody production and cytokine secretion by CD4 + T cells were impaired (44). The fact that miR-155-deficient mice were able to clear primary salmonellosis indicates that innate and CD4 + T-cell function is at least partially functional (43,45,46). In this infection model, antibody production of switched isotypes is T-cell dependent (45); whether the impaired antibody production observed in this study was B-cell intrinsic was not investigated.…”

Immunity to intestinal pathogens: lessons learned from Salmonella

“…Highly susceptible mice can resolve primary infection with attenuated Salmonella strains and this requires a functioning immune system that can develop a CD4 + Th1 cell response and IFN-c production to activate infected macrophages (72)(73)(74)(75). Similar experiments using attenuated bacterial strains show that mice lacking B cells resolve primary infection with similar kinetics to wildtype mice (76,77), indicating that B-cell responses do not participate in primary clearance.…”