Host Defense against Bacterial Infection and Bacterial Toxin-induced Impairment of Innate Immunity

Abstract

Whereas granulopoiesis during Gram-negative bacterial infection is accelerated through activation of toll-like receptor 4 (TLR4), it has not been elucidated whether Gram-positive bacterial infection can stimulate granulopoiesis. Using the well-known TLR2 agonist peptidoglycan (PGN), it was shown that neutrophils in bone marrow and spleen and plasma granulocyte colony-stimulating factor were increased in mice that had received intraperitoneal administration of PGN. Incorporation of bromodeoxyuridine into bone marrow neutrophils increased in mice administered PGN, demonstrating that PGN promotes granulopoiesis. These results illustrate that bacterial recognition by TLR2 facilitates granulopoiesis during Gram-positive bacterial infection. Thus, granulopoiesis is accelerated to suppress bacterial infection, but some bacteria can still cause severe infections. Clostridium perfringens is a Gram-positive, anaerobic pathogenic bacterium and causes life-threatening gas gangrene in humans. Of the many toxins produced by C. perfringens, α-toxin is known to be a major virulence factor during infection. Recently, it has been revealed that C. perfringens α-toxin impairs the innate immune system by inhibiting neutrophil differentiation, which is crucial for the pathogenesis of C. perfringens. Moreover, the toxin also attenuates erythropoiesis, which would cause severe anemia in clinical settings. The findings provide new insight to understand how hosts strengthen innate immunity to fight pathogenic bacteria and how they evade the hosts' immune systems.