{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:56:42Z","timestamp":1791946602436,"version":"4.3.4"},"reference-count":217,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Human genetic control is thought to affect a considerable part of the outcome of infection with<jats:italic>Mycobacterium tuberculosis<\/jats:italic>(<jats:italic>Mtb<\/jats:italic>). Most of us deal with the pathogen by containment (associated with clinical \u201clatency\u201d) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to<jats:italic>Mtb<\/jats:italic>infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and<jats:italic>Mtb<\/jats:italic>which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during<jats:italic>Mtb<\/jats:italic>infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of<jats:italic>Mtb<\/jats:italic>infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to<jats:italic>Mtb<\/jats:italic>but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to \u2018effectors\u2019 like IFN-\u03b3, IL-12, Nitric Oxide and TNF that are critical for<jats:italic>Mtb<\/jats:italic>control, \u2018sensors\u2019 like PRRs are less critical for the outcome of<jats:italic>Mtb<\/jats:italic>infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that<jats:italic>Mtb<\/jats:italic>rarely goes unnoticed. Genetic association studies investigating PRRs during<jats:italic>Mtb<\/jats:italic>infection should therefore be designed to investigate endophenotypes of infection \u2013 such as immunological or clinical variation \u2013 rather than just TB disease, if we hope to understand the molecular interface between innate immunity and<jats:italic>Mtb<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2021.714808","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T07:09:19Z","timestamp":1625036959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Underwhelming or Misunderstood? 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