Alternatively Activated and Immunoregulatory Monocytes in Human Filarial Infections

• Published in: The Journal of infectious diseases Vol. 199; no. 12; pp. 1827 - 1837
• Main Authors: Babu, Subash , Kumaraswami, V. , Nutman, Thomas B.
• Format: Journal Article
• Language: English
• Published: Oxford University of Chicago Press 15.06.2009; Oxford University Press
• Subjects: Animals; Antigens; Antigens, Helminth - immunology; Arginase - genetics; Arginase - metabolism; Biological and medical sciences; Brugia malayi; Brugia malayi - immunology; Cohort Studies; Complement Pathway, Alternative; Cytokines; Cytokines - genetics; Cytokines - metabolism; Diseases caused by nematodes; Down-Regulation; Filariases; Filariasis - immunology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - immunology; Genes; Helminthic diseases; Humans; Infections; Infectious diseases; Lymphatic filariases; Macrophages; Medical sciences; Messenger RNA; Microbiology; Monocytes; Monocytes - classification; Monocytes - immunology; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Parasites; Parasitic diseases; Phenotypes; Tuberculin; Up-Regulation; Human; Infection; Microbiology; Monocyte; Nematode disease; Parasitosis; Filariosis; Helminthiasis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/599090

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 β, 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.