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

Ngiambudulu M Francisco; Nasiema Allie; Boipelo Sebesho; Bernhard Ryffel; Muazzam Jacobs

doi:10.22038/ijbms.2020.37947.9021

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

Iran J Basic Med Sci. 2020 May;23(5):680-690. doi: 10.22038/ijbms.2020.37947.9021.

Authors

Ngiambudulu M Francisco^{1

2

3}, Nasiema Allie⁴, Boipelo Sebesho⁵, Bernhard Ryffel⁶, Muazzam Jacobs^{5

7

8}

Affiliations

¹ Program of Infection and Immunity, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
² Institute of Tuberculosis Control, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
³ Key Laboratory of Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
⁴ SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁵ Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
⁶ Institut de Transgenose, CNRS, GEM2358, Orleans, France, University of Orleans and CNRS UMR7355, Experimental and Molecular Immunology and Neurogenetics, Orleans, France.
⁷ National Health Laboratory Service, Sandringham, Johannesburg, South Africa.
⁸ Immunology of Infectious Disease Research Unit, South African Medical Research Council, Cape Town 8000, South Africa.

Abstract

Objectives: 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.

Keywords: Antibody; Central nervous system; Humoral; Immunity infections; Mycobacterium; Tumor necrosis factor.