Resistance to infection in murine beta-thalassemia.
Clinical evidence suggests that individuals with chronic iron overload may be at increased risk of bacterial infection. We studied this question by using a unique model in which mice homozygous for a deletion in the gene encoding for the beta-major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to beta-thalassemia in humans. Mice heterozygous for the gene deletion were phenotypically normal. Homozygous mice were significantly more susceptible to infection with Listeria monocytogenes than were heterozygous mice (P less than 0.01). This increased susceptibility was associated with a greater number of organisms in the liver and spleen than was found in heterozygous mice (P less than 0.05). However, histologic studies demonstrated similar inflammatory responses within these organs in homozygous and heterozygous mice. The increased susceptibility of homozygous mice to infection with L. monocytogenes was not seen when homozygotes were immunized with a low dose of L. monocytogenes. Although the results were not as striking as with L. monocytogenes, homozygous mice were also found to be more susceptible to infection with Salmonella typhimurium than were heterozygous mice (P less than 0.05). Splenic mononuclear cells from homozygous mice demonstrated less responsiveness in vitro to the mitogens concanavalin A and phytohemagglutinin than did those from heterozygotes (P less than 0.05). These data suggest that there is a generalized defect in innate immunity in homozygous mice which makes them more susceptible to infection by L. monocytogenes and S. typhimurium. The site of this immunological defect is not known but is most likely in the mononuclear phagocyte and may be due to tissue iron overload.
Ampel
N M
NM
Veterans Administration Medical Center, Tucson, Arizona.
Van Wyck
D B
DB
Aguirre
M L
ML
Willis
D G
DG
Popp
R A
RA
D000818:Animals; D005260:Female; D007113:Immunity, Innate; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013158:Splenic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013789:Thalassemia / Q000235:genetics / Q000276:immunology*