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

• Main Authors: Ngiambudulu Francisco, Nasiema Allie, Boipelo Sebesho, Bernhard Ryffel, Muazzam Jacobs
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-05-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: antibody; central nervous system; humoral; immunity infections; mycobacterium; tumor necrosis factor
• Online Access: http://ijbms.mums.ac.ir/article_15228_8c80a7efd44173f1738137108131952d.pdf

<em><strong>Objective(s):</strong> </em>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).<br /><em><strong>Materials and Methods:</strong></em> 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. <br /><em><strong>Results:</strong></em> 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.<br /><em><strong>Conclusion:</strong></em> 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.