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

Ageing increases susceptibility to infectious diseases including tuberculosis. Limited literature is available on the perturbed cellular details in aged (>60 years) TB patients and understanding their molecular pathways is critical. In this study, C57BL/6 mice of multiple age groups; 2, 5, 9, 17 months (M), were aerosol infected with 100-120 colony forming unit (cfu) of Mycobacterium tuberculosis (Mtb) H37Rv and treated with rifampicin and isoniazid. Tissue (lungs, spleen, and liver) bacterial burden were monitored by cfu assay, liver micronutrients profiled using mass spectrometry, and tissue immune cell phenotyping was carried out employing flow cytometry. Interestingly, at 6 weeks post infection (w.p.i.), older mice (5, 9, 17M) showed similar tissue mycobacterial loads as compared to younger ones (2M). However, a delayed lung mycobacterial clearance was observed at 2 weeks post treatment in a subset of aged (17M) mice. Mtb infection led to decreased liver Fe, Zn and Se levels in 2M mice with minimum variations in 17M mice. Healthy 17M mice had higher frequency of splenic CD4+CD44+CXCR5+, CD4+CD44+PD1+, CD4+CXCR5+PD1+ and T-follicular helper (TFH; CD4+CD44+CXCR5+PD1+) cells. Aged C57BL/6 mice showed a significant decline in the frequency of CD4+CD44+CXCR5+ cells with infection progression, which might be contributing to the delayed Mtb clearance. Further characterization of TFH cell subsets, after careful validation, may provide insights for adjunct therapeutic development for benefitting the aged TB patients. ### Competing Interest Statement The authors have declared no competing interest.