Group B streptococcus-induced nitric oxide production in murine macrophages is CR3 (CD11b/CD18) dependent

Abstract

Nitric oxide (NO) is produced by murine macrophages in response to cytokines and/or gram-negative bacterial lipopolysaccharide. NO induction by gram-positive bacteria such as group B streptococci (GBS), the major etiologic agents of neonatal pneumonia and meningitis, has received little study. GBS as well as two other gram-positive bacterial species, Staphylococcus aureus and Staphylococcus epidermnidis, were found to stimulate NO production in thioglycolate-elicited murine macrophages and in the mouse macrophage cell line J774A.1 in the presence of gamma interferon. Serotype Ia and m GBS were both stimulatory, as were asialoand type antigen-deficient mutant strains of type III GBS. NO production was dose dependent, inhibitable by L-arginine analogs, and unaffected by polymyxin B. Since phagocytosis by murine and human phagocytes of GBS is dependent on complement receptor type 3 (CR3), the role of CR3 in the NO response to GBS was tested in the CR3-deficient myelomonocytic cell line WEHI-3. GBS did not induce NO, whereas S. aureus or lipopolysaccharide did induce NO in WEEHI-3 cells. S. epidermidis, whose nonopsonic phagocytosis is also CR3 dependent, failed to induce NO in WEHI-3 cells. Monoclonal anti-CR3 (anti-CD11b or anti-CD18) in the presence of interferon also induced NO production in thioglycolate-elicited macrophages and in J774A.1 cells but not in WEEHI-3 cells. This evidence suggests that ligated CR3 and gamma interferon act synergistically to induce NO production and that CR3 mediates the GBS-induced signal for NO production in interferon-treated macrophages.

Differential regulation of lipopolysaccharide and Gram‐positive bacteria induced cytokine and chemokine production in macrophages by Gαi proteins

“…Two membrane proteins, the integrin b 2 CD11b/CD18 (CR3) and CD14 have been suggested as integral parts of the innate immune response to GBS. 22,30 However, CD11b/ CD18 has no known inflammatory signalling capabilities. 31 CD14 is known to interact with TLRs.…”

Endothelial Cell Injury Caused by Candida albicans Is Dependent on Iron

“…A potential mechanism by which iron chelation may protect endothelial cells from injury by C. albicans is by inhibiting the activity of inducible nitric oxide synthase. Phagocytosis has been found to stimulate the activity of this iron-dependent enzyme in host cells (13). Therefore, it is possible that the phagocytosis of C. albicans induces nitric oxide synthase activity in endothelial cells.…”

Cytokine Response to Group B Streptococcus Infection in Mice

“…For example, a previous report examining the role of complement in determining the phagocytosis of GBS-III by peritoneal murine macrophages in the absence of immune serum, has underlined that C3-dependent binding may be important for mononuclear phagocyte-dependent clearance of GBS from the blood of patients with a deficiency of type-specific antibodies [60]. Other authors, on the basis of results obtained in an animal model of in vitro GBS-III infection, have suggested that activation of NK cells with IFN-g release could be a critical event, during in vivo infection, in promoting bactericidal functions of neutrophils and macrophages [51,61,62]. Contrary to these speculations, in our experimental model, the increase of important functions of the natural immune system, such as splenic NK activity and microbicidal activity of splenic mononuclear and polymorphonuclear phagocytes induced in vivo by GBS-Ia, did not seem to have any effect on resistance to infection, which in fact rapidly became lethal.…”