Persistence of gut mucosal innate immune defenses by enteric α-defensin expression in the simian immunodeficiency virus model of AIDS

Melinda M. Zaragoza, Sumathi Sankaran-Walters, Don R. Canfield, Jason K S Hung, Enrique Martinez, André J. Ouellette, Satya Dandekar

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Gastrointestinal mucosa is an early target of HIV and a site of viral replication and severe CD4+ T cell depletion. However, effects of HIV infection on gut mucosal innate immune defense have not been fully investigated. Intestinal Paneth cell-derived α-defensins constitute an integral part of the gut mucosal innate defense against microbial pathogens. Using the SIV-infected rhesus macaque model of AIDS, we examined the level of expression of rhesus enteric α-defensins (REDs) in the jejunal mucosa of rhesus macaques during all stages of SIV infection using real-time PCR, in situ hybridization, and immunohistochemistry. An increased expression of RED mRNAs was found in PC at the base of the crypts in jejunum at all stages of SIV infection as compared with uninfected controls. This increase correlated with active viral replication in gut-associated lymphoid tissue. Loss of RED protein accumulation in PC was seen in animals with simian AIDS. This was associated with the loss of secretory granules in PC, suggesting an increase in degranulation during advanced SIV disease. The α-defensin-mediated innate mucosal immunity was maintained in PC throughout the course of SIV infection despite the mucosal CD4+ T cell depletion. The loss of RED protein accumulation and secretion was associated with an increased incidence of opportunistic enteric infections and disease progression. Our findings suggest that local innate immune defense exerted by PC-derived defensins contributes to the protection of gut mucosa from opportunistic infections during the course of SIV infection.

Original languageEnglish (US)
Pages (from-to)1589-1597
Number of pages9
JournalJournal of Immunology
Volume186
Issue number3
DOIs
StatePublished - Feb 1 2011

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Defensins
Simian Immunodeficiency Virus
Acquired Immunodeficiency Syndrome
Mucous Membrane
Opportunistic Infections
Infection
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome
Paneth Cells
T-Lymphocytes
Mucosal Immunity
Secretory Vesicles
Lymphoid Tissue
Jejunum
Innate Immunity
HIV Infections
In Situ Hybridization
Disease Progression
Real-Time Polymerase Chain Reaction
Proteins

ASJC Scopus subject areas

  • Immunology

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Persistence of gut mucosal innate immune defenses by enteric α-defensin expression in the simian immunodeficiency virus model of AIDS. / Zaragoza, Melinda M.; Sankaran-Walters, Sumathi; Canfield, Don R.; Hung, Jason K S; Martinez, Enrique; Ouellette, André J.; Dandekar, Satya.

In: Journal of Immunology, Vol. 186, No. 3, 01.02.2011, p. 1589-1597.

Research output: Contribution to journalArticle

Zaragoza, Melinda M. ; Sankaran-Walters, Sumathi ; Canfield, Don R. ; Hung, Jason K S ; Martinez, Enrique ; Ouellette, André J. ; Dandekar, Satya. / Persistence of gut mucosal innate immune defenses by enteric α-defensin expression in the simian immunodeficiency virus model of AIDS. In: Journal of Immunology. 2011 ; Vol. 186, No. 3. pp. 1589-1597.
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