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PLoS Negl Trop Dis. 2012;6(10):e1830. doi: 10.1371/journal.pntd.0001830. Epub 2012 Oct 4.

Evidence of microbial translocation associated with perturbations in T cell and antigen-presenting cell homeostasis in hookworm infections.

Author information

1
National Institutes of Health, International Center for Excellence in Research, Chennai, India.

Abstract

BACKGROUND:

Microbial translocation (MT) is the process by which microbes or microbial products translocate from the intestine to the systemic circulation. MT is a common cause of systemic immune activation in HIV infection and is associated with reduced frequencies of CD4(+) T cells; no data exist, however, on the role of MT in intestinal helminth infections.

METHODS:

We measured the plasma levels of MT markers, acute-phase proteins, and pro- and anti-inflammatory cytokines in individuals with or without hookworm infections. We also estimated the absolute counts of CD4(+) and CD8(+) T cells as well as the frequencies of memory T cell and dendritic cell subsets. Finally, we also measured the levels of all of these parameters in a subset of individuals following treatment of hookworm infection.

RESULTS:

Our data suggest that hookworm infection is characterized by increased levels of markers associated with MT but not acute-phase proteins nor pro-inflammatory cytokines. Hookworm infections were also associated with increased levels of the anti-inflammatory cytokine--IL-10, which was positively correlated with levels of lipopolysaccharide (LPS). In addition, MT was associated with decreased numbers of CD8(+) T cells and diminished frequencies of particular dendritic cell subsets. Antihelmintic treatment of hookworm infection resulted in reversal of some of the hematologic and microbiologic alterations.

CONCLUSIONS:

Our data provide compelling evidence for MT in a human intestinal helminth infection and its association with perturbations in the T cell and antigen-presenting cell compartments of the immune system. Our data also reveal that at least one dominant counter-regulatory mechanism i.e. increased IL-10 production might potentially protect against systemic immune activation in hookworm infections.

PMID:
23056659
PMCID:
PMC3464301
DOI:
10.1371/journal.pntd.0001830
[Indexed for MEDLINE]
Free PMC Article

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