Tuberculosis endotypes to guide stratified host-directed therapy

Andrew R. DiNardo, Tomoki Nishiguchi, Sandra L. Grimm, Larry S. Schlesinger, Edward A. Graviss, Jeffrey D. Cirillo, Cristian Coarfa, Anna M. Mandalakas, Jan Heyckendorf, Stefan H.E. Kaufmann, Christoph Lange, Mihai G. Netea, Reinout Van Crevel

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations


There is hope that host-directed therapy (HDT) for tuberculosis (TB) can shorten treatment duration, help cure drug-resistant disease, or limit immunopathology. Many candidate HDT drugs have been proposed, but solid evidence only exists for a few select patient groups. The clinical presentation of TB is variable, with differences in severity, tissue pathology, and bacillary burden. TB clinical phenotypes likely determine the potential benefit of HDT. Underlying TB clinical phenotypes, there are TB “endotypes,” defined as distinct molecular profiles, with specific metabolic, epigenetic, transcriptional, and immune phenotypes. TB endotypes can be characterized by either immunodeficiency or pathologic excessive inflammation. Additional factors, such as comorbidities (HIV infection, diabetes, helminth infection), structural lung disease, or mycobacterial virulence also drive TB endotypes. Precise disease phenotyping, combined with in-depth immunologic and molecular profiling and multimodal omics integration, can identify TB endotypes, guide endotype-specific HDT, and improve TB outcomes, similar to advances in cancer medicine.

Original languageEnglish (US)
Pages (from-to)217-232
Number of pages16
Issue number3
StatePublished - Mar 12 2021


  • endotypes
  • immune correlates of protection
  • tuberculosis

ASJC Scopus subject areas

  • Medicine(all)


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