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

George, P.J.; Anuradha, R.; Kumar, N.P.; Kumaraswami, V.; Nutman, T.B.; Babu, S.

PLOS Neglected Tropical Diseases; 2012; 6; e1830.

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.

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