Alessandra Ricciardi1, Thomas B Nutman1. 1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Abstract
BACKGROUND: 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 mf positive (mf+) and mf negative (mf-) 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+ individuals had significantly increased filarial antigen-driven IL-24, and IL-19 compared to mf- subjects. Mf+ patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf- patients. T cell expression of IL-19 and IL-24 by 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. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: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 loiasispatients 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 mf positive (mf+) and mf negative (mf-) 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+ individuals had significantly increased filarial antigen-driven IL-24, and IL-19 compared to mf- subjects. Mf+ patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf- patients. T cell expression of IL-19 and IL-24 by 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. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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