Distinct Effects of Integrins αXβ2 and αMβ2 on Leukocyte Subpopulations during Inflammation and Antimicrobial...

Integrins α_Mβ₂ and α_Xβ₂ are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although α_Mβ₂ was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of α_Xβ₂ remain largely obscure. Here, we tested the ability of mice deficient in integrin α_Mβ₂ or α_Xβ₂ to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of α_Mβ₂ affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and α_Mβ₂-deficient PMN displayed defective inflammatory functions. In contrast, deficiency of α_Xβ₂ 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 α_Xβ₂ 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 α_Mβ₂ 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 α_Xβ₂, but not of α_Mβ₂, increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that α_Mβ₂ plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of Mϕ, whereas α_Xβ₂ is central in the regulation of inflammatory functions of recruited and tissue-resident Mϕ.