Microfold Cells Actively Translocate Mycobacterium tuberculosis to Initiate Infection

Vidhya R. Nair, Luis H. Franco, Vineetha M. Zacharia, Haaris S. Khan, Chelsea E. Stamm, Wu You, Denise K. Marciano, Hideo Yagita, Beth Levine, Michael U. Shiloh

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The prevailing paradigm is that tuberculosis infection is initiated when patrolling alveolar macrophages and dendritic cells within the terminal alveolus ingest inhaled Mycobacterium tuberculosis (Mtb). However, definitive data for this model are lacking. Among the epithelial cells of the upper airway, a specialized epithelial cell known as a microfold cell (M cell) overlies various components of mucosa-associated lymphatic tissue. Here, using multiple mouse models, we show that Mtb invades via M cells to initiate infection. Intranasal Mtb infection in mice lacking M cells either genetically or by antibody depletion resulted in reduced invasion and dissemination to draining lymph nodes. M cell-depleted mice infected via aerosol also had delayed dissemination to lymph nodes and reduced mortality. Translocation of Mtb across two M cell transwell models was rapid and transcellular. Thus, M cell translocation is a vital entry mechanism that contributes to the pathogenesis of Mtb.

Original languageEnglish (US)
Pages (from-to)1253-1258
Number of pages6
JournalCell Reports
Volume16
Issue number5
DOIs
StatePublished - Aug 2 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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