The role of β2 integrins in host responses to intracellular bacterial infection in mice (50.27)

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 for β2 integrins in host defense, CD11a, CD11b and CD11c deficient and wildtype mice were infected with Listeria monocytogenes (LM). Surprisingly, the absence of the integrins had no effect on the expansion of antigen specific CD8 T cells in response to infection with LM. Although CD11b-/- and CD11c-/- exhibited normal effector functions, granzyme levels and effector cytokines were reduced in CD11a-/- CD8 T cells as compared to WT CD8 T cells post LM infection. CD11b and CD11c are also highly expressed by important antigen presenting cells such as macrophages and dendritic cells (DC). Therefore, we tested whether the absence of CD11c or CD11b compromised DC function. However, preliminary experiments indicated that upon infection, CD11b-/- and CD11c-/- DCs are capable of normal activation and migration. Overall, these results suggested that unlike CD11b and CD11c, CD11a may play an integral role in induction of optimal effector functions in CD8 T cells.