The Role of BCG/PPD‐Activated Macrophages in Resistance against Systemic Candidiasis in Mice

Abstract

The main conclusions of this study are that BCG/PPD-activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA-induced production of H2O2, kill about one-third of the phagocytosed Candida albicans, and cause more than 50% inhibition of the intracellular formation of germ tubes by C. albicans. Peritoneal macrophages from mice that were colonized post-natally with C. albicans do not show increased production of H2O2 upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree. These macrophages are capable of killing about 20% of the ingested C. albicans. In vivo, the number of Candida in the kidney, spleen and liver after intravenous injection of Candida albicans is significantly lower in BCG-treated mice than in control mice. Post-natal colonization with C. albicans has only a limited effect on the outgrowth of intravenously injected C. albicans in the spleen and liver but does not influence growth in the kidney. These results indicate that acquired immunity against a systemic Candida infection involves both oxidative and non-oxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of C. albicans.

B Cells Are Not Essential for Lactobacillus-Mediated Protection against Lethal Pneumovirus Infection

“…Among these findings, as noted earlier, were observations documenting systemic exposure to attenuated Mycobacterium tuberculosis , (BCG vaccination) that resulted in non-specific systemic immunity to several unrelated pathogens (reviewed in [6]). BCG-mediated macrophage activation and anti-microbial peroxide production was initially implicated in this mechanism [26]. Kleinnijenhuis and colleagues [27] recently reported that non-specific protection elicited by BCG vaccination in human subjects was directly dependent on persistent, NOD2-dependent epigenetic alterations in circulating monocytes, specifically, specifically, altered histone methylation patterns, and that BCG-vaccination likewise elicited induction of proinflammatory cytokines IFNγ, TNFα and IL-1β.…”

Trained immunity: A program of innate immune memory in health and disease

“…Compelling evidence that trained immunity is induced in vertebrates and mediates at least some of the protective effects of vaccination came from studies showing that immunization of mice with bacillus Calmette Guerin (BCG, the tuberculosis vaccine that is also the most commonly used vaccine worldwide), induces T cell-independent protection against secondary infections with Candida albicans or Schistosoma mansoni (22, 23). The hypothesis that trained immunity can be elicited in vertebrates is further supported by studies investigating the mechanism of protection against disseminated candidiasis conferred by attenuated strains of C. albicans .…”

Innate immune memory: An evolutionary perspective

“…Compelling evidence that trained immunity may mediate at least some of the protective effects of vaccination has come from studies showing that vaccination of animals with bacillus Calmette Guerin (BCG), the tuberculosis vaccine that is also the most commonly used vaccine worldwide, induces T‐cell independent protection against secondary infections with C. albicans or Schistosoma mansoni . These data are complemented by studies investigating the mechanism of protection against disseminated candidiasis conferred by attenuated strains of C. albicans .…”