Human lung mucosal and serum IgG antibody responses against cell wall components of Mycobacterium tuberculosis
Clemens Hermann (1,2), Malika Davids (3), Muneerah Smith (2), Anil Pooran (3), Keertan Dheda (3,4), Jonathan M Blackburn (2)
(1) Immune Cell Biology Laboratory, Department of Biomedicine, University of Basel, University Hospital of Basel, Basel, Switzerland
(2) Department of Integrative Biomedical Sciences, Institute of Infectious Disease & Molecular
Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
(3) Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa
(4) Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
Better understanding of mucosal immune responses against infection with Mycobacterium tuberculosis (Mtb) is urgently needed to control of the current Tuberculosis epidemic. While cell-mediated immunity is crucial in controlling Mtb infection, recent studies have highlighted the potential role of antibodies, especially antibodies against surface-exposed Mtb antigens. However, knowledge of Mtb-specific antibody responses in the human lung mucosa during infection is missing.
Using a human lung-challenge model in subjects with a spectrum of pre-existing mycobacterial exposure, we assessed for the first time the reactivity of lung mucosal IgG antibodies against protein and lipid components of the mycobacterial cell wall using microarray technology. After a 3-day intra-lung challenge with either live M. bovis BCG or purified protein derivative (PPD), we find strong antibody responses in bronchoalveolar lavage fluid against Mtb cell wall proteins and polysaccharides as well as some glycolipid antigens. We show that antibody responses against these antigens were increased with pre-existing mycobacterial exposure. In addition, we find that the antibody response at the mucosal site was remarkably different to the systemic antibody response measured in serum.
Combined, this data highlights the need to assess reactivity of mucosal antibodies responses at the site of infection, rather than in serum, in order to clarify the potential role of antibodies during Mtb infection.