IL-10 and Its Related Superfamily Members IL-19 and IL-24 Provide Parallel/Redundant Immune-Modulation in Loa loa Infection

• Published in: The Journal of infectious diseases Vol. 223; no. 2; pp. 297 - 305
• Main Authors: Ricciardi, Alessandra, Nutman, Thomas B
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 03.02.2021
• Subjects: Antigens; Clinical trials; Cytokines; Flow cytometry; IL-1β; Immunomodulation; Infections; Interleukin 10; Interleukin 13; Interleukin 19; Interleukin 22; Interleukin 24; Interleukin 4; Interleukin 5; Interleukin 9; Leukocytes (mononuclear); Lymphocytes T; Major and Brief Reports; Parasites; Peripheral blood mononuclear cells; cytokine regulation; microfilariae; loiasis; IL-10 superfamily members; T-cell responses
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiaa347

Abstract Background Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied. Methods Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry. Results All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1β. IL-24 production was also regulated by IL-37. Conclusion These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections. Clinical Trials Registration NCT00001230. IL-19 and IL-24 are differentially regulated and expressed in Loa loa infection. Parasite-antigen driven IL-19 and IL-24 production appears to be related to microfilarial positivity and IL-37, IL-10, and IL-1β are important regulators of IL-24 and IL-19 production in loiasis.