Fig 1.
Mtb travels to the thoracic lymph nodes from the lungs.
(1) Infection begins when a person inhales aerosolized droplets containing Mtb. (2) Mtb travels into the lungs and is taken up by phagocytic cells. (3) Mtb is then transported to a thoracic lymph node on the same side of the body. Steps 2 and 3 take 9–11 days in mice. (4) Mtb-containing phagocytic cells present antigen to naïve lymphocytes and generate an immune response. Activated lymphocytes travel back to the lungs to contain Mtb infection. (5) Live Mtb, either shuttled to the lymph nodes by phagocytic cells or carried by lymph fluid, begins to multiply and cause a granuloma to form. Mtb burden increases as the granuloma size increases. Lymph nodes are generally not able to eliminate the infection. CFU, colony forming units; Mtb, Mycobacterium tuberculosis; p.i., post infection.
Fig 2.
Mtb infection results in granuloma formation that disrupts the normal lymph node architecture.
(A) Lymph node showing normal architecture without granuloma formation. (B) Lymph node with partially effacing granulomas. (C) Total nodal effacement by multiple coalescing non-necrotizing granulomas. (D) Near total nodal effacement by multiple coalescing caseous granulomas. Granulomas are outlined with a white line. Measuring bar = 1 mm. Mtb, Mycobacterium tuberculosis.
Fig 3.
Mtb is spread ipsilaterally from the lungs to the thoracic lymph nodes in macaques.
Cynomolgus macaques infected with low dose Mtb necropsied from 10 to 55 weeks post infection were assessed for lung disease by gross pathology during necropsy. Lymph node involvement was determined by quantitative culture for Mtb. The pie charts show the lymph node counts. The proportion is in parenthesis. N = 74 monkeys. LN, lymph node; Mtb, Mycobacterium tuberculosis.
Fig 4.
Latent TB reactivation can start in the lymph nodes.
Mtb resides undetected in lymph nodes during latent Mtb infection or as a result of inadequate drug concentration in lymph nodes during treatment. (1) After latent TB reactivation is induced by HIV infection, CD4 T-cell depletion, or TNF neutralization, non-necrotizing granulomas form adjacent to established and often mineralized granulomas in the lymph nodes. (2) Mtb exits lymph nodes through unknown mechanisms, probably carried by lymph into the subclavian vein and then spreading hematogenously or when the lymph node structure breaks down and delivers bacilli to the airways. (3) Mtb travels to and forms new granulomas in the lungs and other organs (extrapulmonary TB). Mtb, Mycobacterium tuberculosis; TB, tuberculosis; TNF, tumor necrosis factor.