The Non-synonymous rs763780 Single-Nucleotide Polymorphism in IL17F Gene Is Associated With Susceptibility to Tuberculosis and Advanced Disease Severity in Argentina

ROLANDELLI, AGUSTÍN; PELLEGRINI, JOAQUÍN MIGUEL; HERNÁNDEZ DEL PINO, RODRIGO EMANUEL; TATEOSIAN, NANCY LILIANA; AMIANO, NICOLÁS OSCAR; MORELLI, MARÍA PAULA; CASTELLO, FLORENCIA ANDREA; CASCO, NICOLÁS; LEVI, ALBERTO; PALMERO, DOMINGO JUAN; GARCÍA, VERÓNICA EDITH

Frontiers in Immunology

Frontiers Media

Año: 2019 vol. 10

Th17 lymphocytes, that produce IL17A, IL17F and IL22, play a crucial role during the immune19 response against Mycobacterium tuberculosis (Mtb) infection. Whereas the contribution of IL17A in20 immunity to tuberculosis is usually accepted, the role of IL17F has been scarcely studied so far. The21 aim of this work was to evaluate the existence of a potential association of the non-synonymous22 variant rs763780 SNP of the IL17F gene with human tuberculosis. Accordingly, by comparing23 healthy donors (HD) and tuberculosis patients (TB) populations we demonstrated an association24 between the C allele of the SNP and the susceptibility to tuberculosis disease in Argentina.25 Furthermore, we found that peripheral blood mononuclear cells (PBMCs) from individuals with a26 more effective immune response against Mtb secreted the highest levels of IL17F when stimulated27 with a lysate of Mtb (Mtb-Ag). Besides, we evidenced that Mtb-Ag-stimulated PBMCs from HD28 carrying the C variant of the SNP displayed the lowest IFNG secretion, proliferation index and29 SLAM expression as compared to TT carriers. Moreover, Mtb-Ag-stimulated PBMCs from TB30 carrying the C allele produced the lowest levels of IFNG, the highest level of IL17A and the31 minimum proliferation indexes as compared to TT TB, suggesting a relationship between the C allele32 and tuberculosis severity. In fact, TB carrying the C allele presented a more severe disease, with the33 highest bacilli burden in sputum. Together, our findings identify the IL17F rs763780 SNP as a34 biomarker of tuberculosis susceptibility and advanced disease severity in Argentina, suggesting that35 IL17F could be a critical cytokine in tuberculosis immunity.