{"doi":"10.1111/imcb.12402","title":"When it’s good to have MAITs","abstract":"This article discusses mucosal-associated invariant T-cell prophylactic and therapeutic vaccination schemes tested by Sakai et al. in mouse models of Mycobacterium tuberculosis infection together with the outcomes and observations. Tuberculosis (TB) is an old disease with an impressive history of persistent human affliction throughout time. Previous approaches to harness the immune response to Mycobacterium tuberculosis (M. tb), the causative agent of TB, have been largely ineffective at reducing the global burden of TB. Among the new cellular players in bacterial immunity are mucosal-associated invariant T (MAIT) cells. In a recent study published in Mucosal Immunology,1 Sakai et al. examined the MAIT cell response to M. tb and tested preinfection (vaccination) or postinfection (therapeutic) MAIT cell boosting regimens to enhance M. tb clearance in a mouse model. Surprisingly, the authors observed that the timing of the boosted MAIT cell response resulted in profoundly different outcomes for M. tb immunity. Historically, TB was commonly referred to as “consumption,” from the ancient Greek Phthisis, describing the nature of a characteristic “wasting disease.” Improvements in public health and later the emergence of effective antibiotics dramatically reduced the presence of “consumption” in the developed world. Despite these successes, M. tb infections remain the leading cause of mortality from an infectious agent. Moreover, M. tb is highly prevalent, infecting approximately one-quarter of all humans, particularly in the developing world, where a further 10 million diagnoses are made each year. The only vaccine approved for prevention of TB is Bacillus Calmette–Guérin (BCG), a live, attenuated preparation of Mycobacterium bovis which has variable efficacy in humans. Attempts to develop an alternative to the BCG vaccine have been met with criticism for lacking diversity and stagnant development pipelines.2 It is clear that immunity to mycobacterial diseases, including TB, is still poorly understood. While drug therapy remains the gold-standard treatment for TB, the emergence of drug-resistant M. tb has made it increasingly challenging to treat. Thus, renewed effort to resolve the remaining mysteries in our understanding of mycobacterial immunity, described in part for MAIT cells by Sakai et al., may lead us to more informed vaccine design and bring us a step closer to reducing the burden of M. tb infection globally. MAIT cells are a subset of unconventional T cells that recognize small-molecule antigens presented by the evolutionarily conserved and monomorphic major histocompatibility complex class I-like molecule MHC-I-related protein 1 (MR1). In humans, MAIT cells are highly abundant, representing approximately 3% of blood T cells and can be found throughout the peripheral organs.3 MAIT cells are also present, albeit at lower frequencies, in mice and other mammals. The prototypical antigen recognized by MAIT cells is 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil, an intermediary metabolite produced during riboflavin biosynthesis in bacteria and fungi, including M. tb. MAIT cells are multifaceted in their functional response to infections and in maintaining homeostasis, also contributing to tissue repair and wound healing.3 In the context of M. tb, human blood MAIT cell frequencies are reportedly reduced during active infection,4 suggestive of circulating MAIT cell migration into the tissues, although a recent large cohort study disputes this finding.5 Human MAIT cells also secrete interferon-gamma when cultured with M. tb-infected antigen-presenting cells.4 Similarly, in mice, MAIT T-cell receptor transgenic cells secrete interferon-gamma in response to BCG and can inhibit its intracellular growth.6 Moreover, MAIT cells have been shown to offer protective immunity against other respiratory pathogens such as Legionella longbeachae and Francisella tularensis.3 These studies demonstrate that MAIT cells are active during M. tb ","journal":"Immunology and Cell Biology","year":2020,"id":131240,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256187,"name":"James McCluskey","orcid":"0000-0002-8597-815X","position":1,"is_corresponding":false},{"id":256184,"name":"Alexandra J. Corbett","orcid":"0000-0003-1618-4337","position":2,"is_corresponding":false},{"id":584662,"name":"Michael N. T. Souter","orcid":"0000-0002-1459-7923","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-18T23:16:00.235845Z","pmid":"33043485","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}