L-selectin-dependent and -independent homing of naïve lymphocytes through the lung draining lymph node support T cell response to pulmonary Mycobacterium tuberculosis infection

• Published in: PLoS pathogens 2023-07, Vol.19 (7), p.e1011460-e1011460
• Main Authors: Daniel, Lina, Counoupas, Claudio, Bhattacharyya, Nayan D, Triccas, James A, Britton, Warwick J, Feng, Carl G
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Animals; Antigens; B cells; Biology and Life Sciences; Care and treatment; Chemokines; Diagnosis; Growth factors; Health aspects; Homing; Immune response; Infections; Inflammation; Kinases; L-selectin; L-Selectin - metabolism; Lung; Lungs; Lymph Nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Mice; Mycobacterium tuberculosis; Priming; Recruitment; Research and Analysis Methods; Route selection; T cells; T-Lymphocytes; Tuberculosis; Tuberculosis - metabolism; Tuberculosis, Pulmonary; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011460

Recruiting large numbers of naïve lymphocytes to lymph nodes is critical for mounting an effective adaptive immune response. While most naïve lymphocytes utilize homing molecule L-selectin to enter lymph nodes, some circulating cells can traffic to the lung-draining mediastinal lymph node (mLN) through lymphatics via the intermediate organ, lung. However, whether this alternative trafficking mechanism operates in infection and contributes to T cell priming are unknown. We report that in pulmonary Mycobacterium tuberculosis-infected mice, homing of circulating lymphocytes to the mLN is significantly less efficient than to non-draining lymph node. CD62L blockade only partially reduced the homing of naïve T lymphocytes, consistent with L-selectin-independent routing of naïve lymphocytes to the site. We further demonstrated that lymphatic vessels in infected mLN expanded significantly and inhibiting lymphangiogenesis with a vascular endothelial growth factor receptor 3 kinase inhibitor reduced the recruitment of intravenously injected naïve lymphocytes to the mLN. Finally, mycobacterium-specific T cells entering via the L-selectin-independent route were readily activated in the mLN. Our study suggests that both L-selectin-dependent and -independent pathways contribute to naïve lymphocyte entry into mLN during M. tuberculosis infection and the latter pathway may represent an important mechanism for orchestrating host defence in the lungs.