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J Infect Dis. 2009 Jun 15;199(12):1827-37. doi: 10.1086/599090.

Alternatively activated and immunoregulatory monocytes in human filarial infections.

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1
National Institutes of Health-International Center for Excellence in Research, Chennai, India. sbabu@mail.nih.gov

Abstract

BACKGROUND:

Monocytes/macrophages from filaria-infected animals exhibit an alternatively activated phenotype; however, very little is known about the alternative activation phenotype of monocytes in human filarial infection.

METHODS:

To elucidate the activation and cytokine profile of monocytes in human filarial infection, we examined the expression patterns of genes encoding arginase, nitric oxide synthase 2, alternative activation markers, and cytokines in monocytes from individuals with asymptomatic filarial infection and individuals without filarial infection, ex vivo and in response to filarial antigen (Brugia malayi antigen [BmA]).

RESULTS:

Monocytes from patients with asymptomatic filarial infection exhibited significantly diminished expression of NOS2 and significantly enhanced expression of ARG1. These changes were associated with significantly increased expression of the genes encoding resistin, mannose receptor C type 1 (MRC1), macrophage galactose type C lectin (MGL), and chemokine ligand 18 (CCL18). In response to BmA, purified monocytes from infected individuals also expressed significantly lower levels of interleukin (IL)-12 and IL-18 but, in contrast, expressed significantly higher levels of transforming growth factor beta, IL-10, and suppressor of cytokine signaling 1 mRNA. Inhibition of arginase-1 resulted in significantly diminished expression of the genes encoding resistin, MRC1, MGL, and CCL18, as well as significantly enhanced expression of NOS2 and the genes encoding IL-12 and IL-18.

CONCLUSION:

Patent human filarial infection is associated with the presence of monocytes characterized by an alternatively activated immunoregulatory phenotype.

Comment in

PMID:
19456233
PMCID:
PMC3440875
DOI:
10.1086/599090
[Indexed for MEDLINE]
Free PMC Article
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