%0 Journal Article %T Complete ablation of tumor necrosis factor decreases the production of IgA, IgG, and IgM in experimental central nervous system tuberculosis %J Iranian Journal of Basic Medical Sciences %I Mashhad University of Medical Sciences %Z 2008-3866 %A Francisco, Ngiambudulu %A Allie, Nasiema %A Sebesho, Boipelo %A Ryffel, Bernhard %A Jacobs, Muazzam %D 2020 %\ 05/01/2020 %V 23 %N 5 %P 680-690 %! Complete ablation of tumor necrosis factor decreases the production of IgA, IgG, and IgM in experimental central nervous system tuberculosis %K antibody %K Central nervous system %K Humoral %K Immunity infections %K Mycobacterium %K Tumor necrosis factor %R 10.22038/ijbms.2020.37947.9021 %X 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 (TNFf/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 TNFf/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 TNFf/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. %U https://ijbms.mums.ac.ir/article_15228_8c80a7efd44173f1738137108131952d.pdf