The differential roles of LFA-1 and Mac-1 in host defense against systemicinfection with Streptococcus pneumoniae

Mice deficient in CD18, which lack all four CD11 integrins, have leukocytos is and increased susceptibility to bacterial infection. To determine the ef fect of deficiencies in LFA-I (CD11a/CD18) or Mac-1 (CD11b/CD18) on host de fense against systemic bacterial infection, knockout mice were inoculated i .p. with Streptococcus pneumoniae. Increased mortality occurred in both LFA -1(-/-) (15 of 17 vs 13 of 35 in wild type (WT), p < 0.01) and Mac-1(-/-) ( 17 of 34 vs 6 of 25, p < 0.01) mice. All deaths in LFA-1(-/-) mice occurred after 72 h, whereas most deaths in Mac-1(-/-) mice occurred within 24-48 h . At 24 h, 21 of 27 Mac-1(-/-) mice were bacteremic, vs 15 of 25 WT (p = 0. 05); no difference was observed between LFA-1(-/-) and WT. Increased bacter ia were recovered from Mac-1(-/-) spleens at 2 h (p = 0.03) and 6 h (p = 0. 002) and from livers (p = 0.001) by 6 h. No difference was observed at 2 h in LFA-1(-/-) mice, but by 6 h increased bacteria were recovered from splee ns (p = 0.008) and livers (p = 0.04). Baseline and peak leukocyte counts we re similar between Mac-1(-/-) and WT, but elevated in LFA-1(-/-). At 8 h, p eritoneal neutrophils were increased in Mac-1(-/-), but not significantly d ifferent in LFA-1(-/-). Histopathologically, at 24 h Mac-1(-/-) animals had bacteremia and lymphoid depletion, consistent with sepsis. LFA-1(-/-) mice had increased incidence of otitis media and meningitis/encephalitis vs WT at 72 and 96 h. Both Mac-1 and LFA-1 play important but distinct roles in h ost defense to S. pneumoniae.