Complete ablation of tumor necrosis factor decreases the production of IgA, IgG, and IgM in experimental central nervous system tuberculosis

OBJECTIVE(S): This study aimed to explore the contribution of tumor necrosis factor (TNF) in the recruitment of B-cell and secretion of immunoglobulins (Igs) during cerebral tuberculosis (TB). MATERIALS AND METHODS: In this work, the contributing role of TNF in regulating Ig secretions was investigated by comparing wild type TNF (TNF(f/f)), B-cell-derived TNF (BTNF(-/-)), and complete TNF ablation (TNF(-/-)) in a mouse cerebral Mycobacterium tuberculosis infection. Using flow cytometry and ELISA, we were able to examine the recruitment of B-cell subsets, and the production of Igs; also assessed the expression of surface markers on B cell subsets. RESULTS: Here, we found that TNF(-/-) mice showed defective expression of IgA, IgG, and IgM antibodies compared with TNF(f/f) and BTNF(-/-) mice, which was significantly decreased in the expression of surface markers and co-stimulatory molecules. Moreover, mice that produced low antibody levels were not able to control infection, therefore progressed to disease; providing direct evidence for the TNF gene-regulating humoral immunity during central nervous system (CNS) M. tuberculosis infection. In contrast, BTNF(-/-) mice controlled the infection and had levels of IgA, IgG, and IgM comparable to TNF(f/f) mice. CONCLUSION: Together, our results demonstrate that TNF may serve as an essential regulator of antibody-mediated immune responses in CNS TB. However, the protective level exhibited by TNF-producing B cells could be defined as baseline protection that could be used in the development of new therapeutic targets or designing new vaccines.