Splenic T follicular helper cells compromise Mycobacterium tuberculosis clearance in aged C57BL/6 mice

Ageing increases susceptibility to infectious diseases like tuberculosis (TB), however limited reports are available on the cellular and molecular details in aged (>60 years) patients. In this study, we asked how low aerosol dose of Mycobacterium tuberculosis H37Rv (Mtb) affects aged (17/19 months; M) C57BL/6 mice in their bacterial clearance, liver micronutrient levels, circulatory cytokines and T cell distribution compared to younger (2/4M) controls. Till 6 weeks post infection, aged mice showed similar tissue (lung, spleen, and liver) Mtb load as young mice. Interestingly, aged mice showed a delayed lung Mtb clearance at 2 weeks post rifampicin (RIF) - isoniazid (INH) treatment compared to younger mice. Aged mice showed unregulated liver Fe levels upon Mtb infection while young mice had lower Fe levels. Aged Mtb infected mice revealed a lower proportion of splenic T-follicular helper (TFH) like CD4+ T cells, which provides B cell help in generating high affinity antibodies and immune memory. Aged mice had higher basal circulatory IL-6 levels. Circulatory IFN-γ levels in aged (19M) C57BL/6 mice failed to resolve upon RIF-INH treatment. Splenic CD4+CD44+ T cells of aged mice showed deregulated levels of mitochondrial proteins (4-hydroxy-2-oxoglutarate aldolase and aspartate aminotransferase). Overall, while filling in knowledge gaps on the host age-related responses to Mtb infection and during treatment, this study provides new perspectives for T cell distribution and function, which opens avenue for adjunct therapeutic development for geriatric TB patients. ### Competing Interest Statement The authors have declared no competing interest.