B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic Mycobacterium tuberculosis lung infection in Diversity Outbred mice.

Autor:	Koyuncu D; Rensselaer Polytechnic Institute, Troy, New York, USA., Tavolara T; Wake Forest University, School of Medicine, Winston Salem, North Carolina, USA., Gatti DM; The Jackson Laboratory, Bar Harbor, Maine, USA., Gower AC; Boston University Clinical and Translational Science Institute, Boston, Massachusetts, USA., Ginese ML; Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA., Kramnik I; NIEDL, Boston University, Boston, Massachusetts, USA., Yener B; Rensselaer Polytechnic Institute, Troy, New York, USA., Sajjad U; Wake Forest University, School of Medicine, Winston Salem, North Carolina, USA., Niazi MKK; Wake Forest University, School of Medicine, Winston Salem, North Carolina, USA., Gurcan M; Wake Forest University, School of Medicine, Winston Salem, North Carolina, USA., Alsharaydeh A; Aiforia Inc., Cambridge, Massachusetts, USA., Beamer G; Aiforia Inc., Cambridge, Massachusetts, USA.; Texas Biomedical Research Institute, San Antonio, Texas, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2024 Jul 11; Vol. 92 (7), pp. e0026323. Date of Electronic Publication: 2024 Jun 20.
DOI:	10.1128/iai.00263-23
Abstrakt:	Because most humans resist Mycobacterium tuberculosis infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with M. tuberculosis and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year. Here, we identified features of asymptomatic M. tuberculosis infection by applying computational and statistical approaches to multimodal data sets. Cytokines and anti- M . tuberculosis cell wall antibodies discriminated progressors vs controllers with chronic pulmonary TB but could not classify mice with asymptomatic infection. However, a novel deep-learning neural network trained on lung granuloma images was able to accurately classify asymptomatically infected lungs vs acute pulmonary TB in progressors vs chronic pulmonary TB in controllers, and discrimination was based on perivascular and peribronchiolar lymphocytes. Because the discriminatory lesion was rich in lymphocytes and CD4 T cell-mediated immunity is required for resistance, we expected CD4 T-cell genes would be elevated in asymptomatic infection. However, the significantly different, highly expressed genes were from B-cell pathways (e.g., Bank1 , Cd19 , Cd79 , Fcmr , Ms4a1 , Pax5 , and H2-Ob ), and CD20+ B cells were enriched in the perivascular and peribronchiolar regions of mice with asymptomatic M. tuberculosis infection. Together, these results indicate that genetically controlled B-cell responses are important for establishing asymptomatic M. tuberculosis lung infection. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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