The differential roles of LFA-1 and Mac-1 in host defense against systemic infection with Streptococcus pneumoniae.
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.
Prince
J E
JE
Section of Atherosclerosis, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Brayton
C F
CF
Fossett
M C
MC
Durand
J A
JA
Kaplan
S L
SL
Smith
C W
CW
Ballantyne
C M
CM
D000818:Animals; D001202:Ascitic Fluid / Q000097:blood; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D006801:Humans; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D016920:Meningitis, Bacterial / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008590:Meningoencephalitis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010033:Otitis Media / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification; D016019:Survival Analysis
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen