The role of β2 integrins in host immune responses to bacterial infection (112.26)

Abstract

Abstract β2 (CD18) integrins (CD11a,b,c,d) are important adhesion molecules necessary for leukocyte migration, homing, and cell to cell interactions. CD18-deficiency in humans is characterized by recurrent bacterial infections and poor wound healing, due to defects in leukocyte activation and migration. However, the in vivo role of each of the individual β2 family members is poorly understood. CD11a, CD11b and CD11c are all upregulated on activated CD8 T cells. In order to study the potential role of β2 integrins in host defense, CD11a, CD11b and CD11c deficient and wildtype mice were infected with Listeria monocytogenes (LM). Our results indicate that the absence of CD11b and CD11c had no effect on antigen specific CD8 T cells in response to infection with LM. On the contrary, after infection, antigen specific CD8 T cells in CD11a -/- mice exhibited diminished proliferation and activation resulting in significantly reduced numbers at the peak of the response. Moreover, CD11a KO mice exhibited a reduced differentiation of short lived effectors subset (KLRG1 hi CD127 lo) although cytokine and granzyme B production was unaffected. Interestingly, upon secondary infection with LM, antigen specific memory CD8 T cells in CD11a KO responded robustly. Overall, these results suggest that CD11a plays a crucial role in regulation of primary CD8 T cell effector differentiation, but may be dispensable for secondary responses to Listeria infection.