Mycobacterium tuberculosis-reactive antibodies are influenced by tissue localization and length of infection 9372

Abstract Description Tuberculosis (TB) remains the top infectious disease killer globally in part because of an incomplete understanding of host responses to the infectious agent, Mycobacterium tuberculosis (Mtb). Emerging data highlight the potential importance of antibody-mediated immunity in TB in which cellular host responses have long been the paradigm. These studies have shown the potential of serum antibodies, but few have examined lung antibodies. In a mouse model of Mtb infection, we find Mtb-reactive IgG, IgM, and IgA in murine lungs are elevated compared to serum at week 4. Unlike bulk IgA titers, Mtb reactive IgA, but not IgG or IgM, from the lung negatively link to Mtb burden in the lungs but not the spleen. This suggests the potential for protection via IgA in the lungs at week 4. By week 16, the difference between lung and serum Mtb-reactive titers is greatly reduced. Further contrasting with week 4, week 16 Mtb-reactive IgM from the lung links negatively with lung Mtb burden and IgM from the serum to spleen burden. Together this data highlights the potential for antibody localization to impact Mtb burden at different times of infection and at different locations in the body. By understanding these different host responses, we may be able to better leverage antibodies in future treatments and diagnostics. Funding Sources NIH NIAID 5T32AI005284-44 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)