Aggravated Lyme carditis in CD11a-/- and CD11c-/- mice.
CD18 hypomorph mice expressing reduced levels of the common beta2 integrin chain develop aggravated Lyme carditis, compared to that developed by wild-type (WT) mice, upon infection with the spirochete Borrelia burgdorferi. The enhancement of Lyme carditis in these mice is characterized by increased macrophage infiltration, correlating with augmented expression of the monocyte/macrophage chemoattractant protein 1 (MCP-1). The lack of CD18 results in the deficiency of all beta2 integrins, i.e., CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1/CR3), CD11c/CD18 (p150,95/CR4), and CD11d/CD18. To determine the roles of the various beta2 integrins in controlling the development of aggravated Lyme carditis, disease induction was analyzed in CD11a-/-, CD11b-/-, and CD11c-/- mice. CD11a-/- and CD11c-/- mice, but not CD11b-/- mice, developed aggravated Lyme carditis after exposure to B. burgdorferi. Similarly to CD18 hypomorph mice, CD11c-/- mice expressed higher levels of MCP-1, compared to both WT and CD11a-/- mice, as determined by in vitro analysis of MCP-1 secretion by bone marrow-derived dendritic cells and in vivo analysis of MCP-1 mRNA expression in B. burgdorferi-infected hearts. On the other hand, CD11a deficiency was associated with heightened heart B. burgdorferi burden relative to that of WT mice. Overall, our results suggest that the increased severity of Lyme carditis in CD18 hypomorph mice is caused by deficiency in CD11a or CD11c, possibly via different mechanisms.
Guerau-de-Arellano
Mireia
M
Department of Pathology, Tufts University School of Medicine, Jaharis 512, 150 Harrison Ave., Boston, MA 02111, USA.
Alroy
Joseph
J
Bullard
Daniel
D
Huber
Brigitte T
BT
D000818:Animals; D018845:CD11 Antigens / Q000235:genetics / Q000502:physiology; D040881:CD11a Antigen / Q000235:genetics* / Q000502:physiology; D039481:CD11b Antigen / Q000235:genetics / Q000502:physiology; D039521:CD11c Antigen / Q000235:genetics* / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D039001:Integrin alpha Chains / Q000235:genetics / Q000502:physiology; D008193:Lyme Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D018845:CD11 Antigens; D040881:CD11a Antigen; D039481:CD11b Antigen; D039521:CD11c Antigen; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D012333:RNA, Messenger