Resistance to infection in murine β-thalassemia

N. M. Ampel, D. B. Van Wyck, M. L. Aguirre, D. G. Willis, R. A. Popp

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Abstract

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 β-major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to β-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 hetrozygous mice (P < 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 < 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 < 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 < 0.05). These data suggest that there is a generalized effect 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 from overload.

Original languageEnglish (US)
Pages (from-to)1011-1017
Number of pages7
JournalInfection and Immunity
Volume57
Issue number4
StatePublished - Jan 1 1989

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Ampel, N. M., Van Wyck, D. B., Aguirre, M. L., Willis, D. G., & Popp, R. A. (1989). Resistance to infection in murine β-thalassemia. Infection and Immunity, 57(4), 1011-1017.