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

J. E. Prince, C. F. Brayton, M. C. Fossett, J. A. Durand, Sheldon Kaplan, C. W. Smith, C. M. Ballantyne

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Mice deficient in CD18, which lack all four CD11 integrins, have leukocytosis and increased susceptibility to bacterial infection. To determine the effect of deficiencies in LFA-1 (CD11a/CD18) or Mac-1 (CD11b/CD18) on host defense 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 bacteria 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 spleens (p = 0.008) and livers (p = 0.04). Baseline and peak leukocyte counts were similar between Mac-1-/- and WT, but elevated in LFA-1-/-. At 8 h, peritoneal neutrophils were increased in Mac-1-/-, but not significantly different 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 host defense to S. pneumoniae.

Original languageEnglish (US)
Pages (from-to)7362-7369
Number of pages8
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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