Toll like receptor (2 and 4) expression and cytokine release by human neutrophils during tuberculosis treatment—A longitudinal study

• Published in: Molecular immunology 2021-12, Vol.140, p.136-143
• Main Authors: J, Nancy Hilda, K, Lucia Precilla, Selvaraj, Anbalagan, Chinnaraj, Saravanan, Luke Elizabeth, Hanna
• Format: Article
• Language: English
• Subjects: Adult; Anti-tuberculosis therapy; Chemokine CCL3 - metabolism; Cytokines; Cytokines - metabolism; Female; Fluorescence; Humans; Interleukin-8 - metabolism; Longitudinal Studies; Male; Mycobacterium tuberculosis; Neutrophils; Neutrophils - metabolism; Toll like receptors; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - metabolism; Tumor Necrosis Factor-alpha - metabolism; Young Adult
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2021.10.009

•Expression of neutrophil TLR2 increases during anti tuberculosis therapy (ATT).•Expression of neutrophil TLR4 remains unaltered during ATT.•Neutrophil secretion of IL-8 and MIP-1a dips and raises during ATT. Host innate immune responses to tuberculosis are poorly explored. Recent findings emphasize the importance of innate cells in working against Mycobacterium tuberculosis, the etiologic agent of this deadly disease. In this study we have tried to learn the role of neutrophils in building up immunity against this pathogen during therapy. We isolated neutrophils from peripheral blood of healthy volunteers and pulmonary tuberculosis patients at different phases of their treatment and cultured them withtoll like receptor ligands overnight. Toll like receptor 2 and 4 expression on neutrophils was analyzed using flow cytometry. The supernatants were used to measure cytokines. We found that in tuberculosis patients, expression of TLR2, a proven receptor of Mycobacterium tuberculosis on neutrophils, was increased throughout the duration of therapy (measured at diagnosis, second month and sixth month of therapy). This demonstrates that TLR2 expression is altered as a result of treatment, but not TLR4. Also, the chemokines IL-8 and MIP1α showed a ‘dip and raise’ fashion as the therapy proceeded. Even though the increase in the pro-inflammatory cytokine secretion by neutrophils seen at the end of therapy is not as expected, it definitely increases our understanding on the function of these cells during TB disease and its resolution and opens new direction in neutrophil research.