Mycobacterium tuberculosis HN878 Infection Induces Human-Like B-Cell Follicles in Mice

José Alberto Choreño-Parra, Suhas Bobba, Javier Rangel-Moreno, Mushtaq Ahmed, Smriti Mehra, Bruce Rosa, John Martin, Makedonka Mitreva, Deepak Kaushal, Joaquín Zúñiga, Shabaana A. Khader

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Specific spatial organization of granulomas within the lungs is crucial for protective anti-tuberculosis (TB) immune responses. However, only large animal models such as macaques are thought to reproduce the morphological hallmarks of human TB granulomas. In this study, we show that infection of mice with clinical "hypervirulent" Mycobacterium tuberculosis (Mtb) HN878 induces human-like granulomas composed of bacilli-loaded macrophages surrounded by lymphocytes and organized localization of germinal centers and B-cell follicles. Infection with laboratory-adapted Mtb H37Rv resulted in granulomas that are characterized by unorganized clusters of macrophages scattered between lymphocytes. An in-depth exploration of the functions of B cells within these follicles suggested diverse roles and the activation of signaling pathways associated with antigen presentation and immune cell recruitment. These findings support the use of clinical Mtb HN878 strain for infection in mice as an appropriate model to study immune parameters associated with human TB granulomas.

Original languageEnglish
Pages (from-to)1636-1646
Number of pages11
JournalJournal of Infectious Diseases
Volume221
Issue number10
DOIs
StatePublished - Apr 27 2020

Keywords

  • B-cell follicles
  • Mycobacterium tuberculosis HN878
  • human granulomatous diseases
  • lung granuloma
  • pulmonary tuberculosis

Fingerprint

Dive into the research topics of 'Mycobacterium tuberculosis HN878 Infection Induces Human-Like B-Cell Follicles in Mice'. Together they form a unique fingerprint.

Cite this