The lupus-susceptibility locus, Sle3, mediates enhanced

Resistance to bacterial infections

Borna Mehrad, Stacy J. Park, Gangaram Akangire, Theodore J. Standiford, Tianfu Wu, Jiankun Zhu, Chandra Mohan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The genetic predisposition to many autoimmune diseases is inherited as a polygenic trait. It is conceivable that some of the causative alleles in these diseases became prevalent in the population by conferring a survival benefit against environmental assaults, such as infections. We used mice cogenic for genetic loci predisposing to systemic lupus erythomatosus to test the hypothesis that some of these genetic loci protect the host from bacterial infections. Mice with the Sle3 lupus-susceptibility locus on a wild-type background were found to have enhanced antibacterial responses in the context of pneumonia and intra-abdominal sepsis than wild-type animals. This was associated with markedly augmented accumulation of neutrophils in infected tissues, and was bone marrow transferable and dependent on the presence of neutrophils, but not lymphocytes. There was no difference in in vitro leukocyte killing of bacteria nor influx of phagocytes between lupus-susceptible and wild-type animals, but neutrophils from lupus-susceptible mice displayed markedly reduced rate of apoptosis, associated with altered expression of Bcl-2 family proteins, contributing to their greater accumulation. Importantly, deliberate inhibition of apoptosis in wild-type animals significantly boosted the accumulation of neutrophils at the site of infection and resulted in an enhanced antimicrobial response. These observations support the concept that some of the genetic loci that mediate autoimmunity may also confer augmented antimicrobial innate immunity.

Original languageEnglish (US)
Pages (from-to)3233-3239
Number of pages7
JournalJournal of Immunology
Volume176
Issue number5
StatePublished - Mar 1 2006

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Bacterial Infections
Wild Animals
Genetic Loci
Neutrophils
Multifactorial Inheritance
Apoptosis
Genetic Predisposition to Disease
Phagocytes
Infection
Autoimmunity
Innate Immunity
Autoimmune Diseases
Sepsis
Pneumonia
Leukocytes
Bone Marrow
Alleles
Lymphocytes
Bacteria
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Mehrad, B., Park, S. J., Akangire, G., Standiford, T. J., Wu, T., Zhu, J., & Mohan, C. (2006). The lupus-susceptibility locus, Sle3, mediates enhanced: Resistance to bacterial infections. Journal of Immunology, 176(5), 3233-3239.

The lupus-susceptibility locus, Sle3, mediates enhanced : Resistance to bacterial infections. / Mehrad, Borna; Park, Stacy J.; Akangire, Gangaram; Standiford, Theodore J.; Wu, Tianfu; Zhu, Jiankun; Mohan, Chandra.

In: Journal of Immunology, Vol. 176, No. 5, 01.03.2006, p. 3233-3239.

Research output: Contribution to journalArticle

Mehrad, B, Park, SJ, Akangire, G, Standiford, TJ, Wu, T, Zhu, J & Mohan, C 2006, 'The lupus-susceptibility locus, Sle3, mediates enhanced: Resistance to bacterial infections', Journal of Immunology, vol. 176, no. 5, pp. 3233-3239.
Mehrad B, Park SJ, Akangire G, Standiford TJ, Wu T, Zhu J et al. The lupus-susceptibility locus, Sle3, mediates enhanced: Resistance to bacterial infections. Journal of Immunology. 2006 Mar 1;176(5):3233-3239.
Mehrad, Borna ; Park, Stacy J. ; Akangire, Gangaram ; Standiford, Theodore J. ; Wu, Tianfu ; Zhu, Jiankun ; Mohan, Chandra. / The lupus-susceptibility locus, Sle3, mediates enhanced : Resistance to bacterial infections. In: Journal of Immunology. 2006 ; Vol. 176, No. 5. pp. 3233-3239.
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