Effect of Human Immunodeficiency Virus Infection on Plasma Bactericidal Activity against Salmonella enterica Serovar Typhimurium

Abstract

b Individuals with human immunodeficiency virus (HIV) infection have increased susceptibility to invasive disease caused by Salmonella enterica serovar Typhimurium. Studies from Africa have suggested that this susceptibility is related in part to the development of a high level of lipopolysaccharide (LPS)-specific IgG that is able to inhibit the killing of S. Typhimurium by bactericidal antibodies in healthy individuals. To explore this issue further, we examined the bactericidal activity against S. Typhimurium using serum and plasma samples from healthy controls and various clinical subgroups of HIV-infected adults in the United States. We found that the bactericidal activity in the samples from HIV-positive elite controllers was comparable to that from healthy individuals, whereas it was significantly reduced in HIV-positive viremic controllers and untreated chronic progressors. As demonstrated previously for healthy controls, the bactericidal activity of the plasma from the elite controllers was inhibited by preincubation with S. Typhimurium LPS, suggesting that it was mediated by anti-LPS antibodies. S. Typhimurium LPS-specific IgG was significantly reduced in all subgroups of HIV-infected individuals. Interestingly, and in contrast to the healthy controls, plasma from all HIV-positive subgroups inhibited in vitro killing of S. Typhimurium by plasma from a healthy individual. Our results, together with the findings from Africa, suggest that multiple mechanisms may be involved in the HIV-induced dysregulation of humoral immunity to S. Typhimurium.

Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection

“…Trebicka et al have recently described the absence of killing of S . Typhimurium by sera from HIV-infected Americans associated with a lack of IgG antibodies to LPS [ 33 ], rather than the high levels of these antibodies that we have found in HIV-infected Africans. This is consistent with the concept that some, but not excessive, antibodies to LPS are required to kill Salmonella .…”

<p>Nontyphoidal <em>Salmonella </em>bacteremia in antiretroviral therapy-na&iuml;ve HIV-infected individuals at three public hospitals in Eastern Ethiopia: prevalence, antimicrobial susceptibility patterns, and associated factors</p>

“…Several immune defects have been contributed to the susceptibility of HIV-infected individuals to NTS bacteremia. These include the depletion of CD4 + , loss of IL-17-producing CD4 + T cells in the gut mucosa,7 and dysregulated excess production of anti-lipopolysaccharide immunoglobulin G that inhibits serum killing of extracellular Salmonella in a concentration-dependent fashion 23,31. In the present study, HIV-infected individuals who had a CD4 + count <200 cells/µL was 3.6 times more likely found to be infected with NTS bacteria (AOR: 3.61, 95% CI: 1.74–5.25).…”

Intestinal Inflammation Leads to a Long-lasting Increase in Resistance to Systemic Salmonellosis that Requires Macrophages But Not B or T Lymphocytes at the Time of Pathogen Challenge

“…Typhimurium as the antigenic target of the bactericidal antibodies, and showed that both serum bactericidal activity and the levels of anti- S . Typhimurium LPS antibodies were significantly reduced in young children and in subsets of HIV-infected adults (10,11). The near-universal presence of antibodies against S .…”