CD39 and immune regulation in a chronic helminth infection: The puzzling case of Mansonella ozzardi

Author(s)

Lima, Nathalia F. ^[1] ; Goncalves-Lopes, Raquel M. ^[1] ; Kruize, Yvonne C. M. ^[2] ; Yazdanbakhsh, Maria ^[2] ; Ferreira, Marcelo U. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Leiden Univ, Med Ctr, Dept Parasitol, Leiden - Netherlands

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 12, n. 3 MAR 2018.
• Web of Science Citations: 2

Abstract

Background Chronic helminth infections typically induce an immunoregulatory environment, with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens. Here we tested whether these changes are also observed in human infections with Mansonella ozzardi, a neglected filarial nematode widely distributed across Latin America. Methods CD4(+) T cell populations from microfilaremic (Fil+) and uninfected (Fil-) inhabitants in M. ozzardi-endemic riverine communities in Brazil were characterized by flow cytometry analysis. Plasma concentrations of a wide range of cytokines and chemokines were measured. We examined whether M. ozzardi infection is associated with suppressed in vitro lympho-proliferative and inflammatory cytokine responses upon stimulation with filarial antigen, unrelated antigens or mitogens. Principal findings/Conclusions Fil+ subjects had lower plasma levels of selected inflammatory cytokines, such as TNF-alpha, IL-8, and IL-6, than their Fil-counterparts. However, we found no evidence for attenuated T-cell responses to filarial antigens or co-endemic pathogens, such as malaria parasites and Toxoplasma gondii. CD4(+) T cells expressing CD39, an ectonucleosidase involved in the generation of the anti-inflammatory molecule adenosine, were increased in frequency in Fil+ subjects, compared to uninfected controls. Significantly, such an expansion was directly proportional to microfilarial loads. Surprisingly, CD39 blocking with a neutralizing antibody suppressed antigen-driven lymphoproliferation in vitro, while decreasing inflammatory cytokine responses, in Fil+ and Fil-individuals. These findings suggest that circulating CD4(+) CD39(+) T cells comprise subsets with both regulatory and stimulatory roles that contribute to the immune homeostasis in chronic M. ozzardi infection. (AU)

• FAPESP's process: 13/12723-7 - Mansonella ozzardi: a neglected filaria that may modulate the immune response to co-occurring infections
• Grantee: Marcelo Urbano Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/26928-0 - Mansonella ozzardi: a neglected filaria that may modulate the immune response to co-occurring infections
• Grantee: Nathália Ferreira Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/06970-0 - Mansonella ozzardi: the neglected New World filarial nematode that can modulate the immune response against concomitant infections
• Grantee: Nathália Ferreira Lima
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate