Abstract
Integrins αMβ2 and αXβ2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αMβ2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αXβ2 remain largely obscure. Here, we tested the ability of mice deficient in integrin αMβ2 or αXβ2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of αMβ2 affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and αMβ2-deficient PMN displayed defective inflammatory functions. In contrast, deficiency of αXβ2 abrogated intraperitoneal recruitment and adhesive functions of monocytes and macrophages (Mϕ) and the ability of these cells to kill/phagocytose Candida albicans or Escherichia coli cells both ex vivo and in vivo During systemic candidiasis, the absence of αXβ2 resulted in the loss of antifungal activity by tissue Mϕ and inhibited the production of tumor necrosis factor alpha (TNF-α)/interleukin-6 (IL-6) in infected kidneys. Deficiency of αMβ2 suppressed Mϕ egress from the peritoneal cavity, decreased the production of anti-inflammatory IL-10, and stimulated the secretion of IL-6. The absence of αXβ2, but not of αMβ2, increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that αMβ2 plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of Mϕ, whereas αXβ2 is central in the regulation of inflammatory functions of recruited and tissue-resident Mϕ.