The MAIT conundrum – how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues

Berkson, Julia D.; Prlic, Martin

doi:10.1016/j.imlet.2017.09.013

Cited by 21 publications

(19 citation statements)

References 72 publications

(90 reference statements)

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“…We measured the frequency of MAIT cells (CD161 hi Vα7.2 + ) within the T cell (CD3 + ) compartment in blood and thoracic duct lymph and found that MAIT cells are present in both ( Figure 1, A and B). Most blood and lymph MAIT cells were CD8 + ( Figure 1B), which is also the most abundant MAIT cell subset in tissues (13).…”

Section: Resultsmentioning

confidence: 97%

“…Once activated, human MAIT cells express IFN-γ and granzyme B (4,5), but a small subset can also secrete IL-17 when stimulated ex vivo (6,7). A decrease in MAIT cell frequencies in the blood has been described in a series of studies including acute and chronic infections, cancer, and autoimmune disorders, indicating that MAIT cells respond and are thus relevant in a wide array of conditions (8)(9)(10)(11)(12)(13)(14). Interestingly, a common theme of these studies is an irreversible decrease or loss of MAIT cells in the blood in chronic infections (HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV]) and autoimmune diseases (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions

Voillet¹,

Buggert²,

Slichter³

et al. 2018

JCI Insight

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Mucosal-associated invariant T cells (MAIT cells) recognize bacterial metabolites as antigen and are found in blood and tissues, where they are poised to contribute to barrier immunity. Recent data demonstrate that MAIT cells located in mucosal barrier tissues are functionally distinct from their blood counterparts, but the relationship and circulation of MAIT cells between blood and different tissue compartments remains poorly understood. Previous studies raised the possibility that MAIT cells do not leave tissue and may either be retained or undergo apoptosis. To directly address if human MAIT cells exit tissues, we collected human donor-matched thoracic duct lymph and blood and analyzed MAIT cell phenotype, transcriptome, and T cell receptor (TCR) diversity by flow cytometry and RNA sequencing. We found that MAIT cells were present in the lymph, despite being largely CCR7- in the blood, thus indicating that MAIT cells in the lymph migrated from tissues and were capable of exiting tissues to recirculate. Importantly, MAIT cells in the lymph and blood had highly overlapping clonotype usage but distinct transcriptome signatures, indicative of differential activation states.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions

Voillet¹,

Buggert²,

Slichter³

et al. 2018

JCI Insight

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“…Moreover, MAIT cells can have both pro-inflammatory as well as tissue repair functions after TCR stimulation and promote accelerated wound healing in the skin 14,16,17 . The inflammatory versus tissue repair functions exerted by MAIT cells are determined by the combination of TCR, cytokine, and costimulatory receptor signals received and are likely dynamically regulated during infection 18 . The current data on MAIT cell responses in vivo are in the context of acute, rapidly resolving infections 12 , and little is understood how MAIT cell function is regulated during the early and late stages of chronic infections such as Mtb.…”

Section: Introductionmentioning

confidence: 99%

MAIT cell-directed therapy of Mycobacterium tuberculosis infection

Sakai

Kauffman

et al. 2021

Mucosal Immunology

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Mucosal-associated invariant T (MAIT) cells are potential targets of vaccination and host-directed therapeutics for tuberculosis, but the role of MAIT cells during Mycobacterium tuberculosis (Mtb) infection in vivo is not well understood. Here we find that following Mtb infection MAIT cells mount minimal responses, and MAIT cell-deficient MR1 −/− mice display normal survival. Preinfection expansion of MAIT cells through 5-OP-RU vaccination fails to protect against subsequent Mtb challenge. In fact, 5-OP-RU vaccination delays Mtb-specific CD4 T cell priming in lung-draining lymph nodes, and conversely MR1 deficiency or blockade accelerates T cell priming. The MAIT cell-mediated delay in T cell priming is partly dependent on TGF-β. Surprisingly, 5-OP-RU treatment during chronic infection drives MAIT cell expansion and an IL-17A-dependent reduction in bacterial loads. Thus, during early infection MAIT cells directly contribute to the notoriously slow priming of CD4 T cells, but later during infection MAIT cell stimulation may be an effective host-directed therapy for tuberculosis.

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“…Intermediates formed during microbial riboflavin biosynthesis also activate MAIT (mucosal-associated invariant T) cells through binding to the MR1 protein of MHC-I molecules on antigen presenting cells (Eckle et al, 2015;Yoshii et al, 2019). However, stimulation by commensal microorganisms are insufficient to fully elicit MAIT cell effector function (Berkson and Prlic, 2017). Thus, commensal bacterial mediated priming of MAIT cells is proposed to contribute to their immunological role in pathogen surveillance, which are then fully activated in the presence of pathogens at sufficient microbial load.…”

Section: Insights and Limitations Of The Predicted Morphological Clasmentioning

confidence: 99%

A Uniquely Altered Oral Microbiome Composition Was Observed in Pregnant Rats With Porphyromonas gingivalis Induced Periodontal Disease

Walkenhorst

Reyes

Pérez

et al. 2020

Front. Cell. Infect. Microbiol.

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Porphyromonas gingivalis is an anaerobic bacterium commonly found in the oral cavity and associated with the development of periodontal disease. P. gingivalis has also been linked to several systemic vascular and inflammatory diseases including poor pregnancy outcomes. Little is known about the changes in the oral flora during pregnancy in connection to P. gingivalis infection. This pilot study aims to explore changes in the oral microbiome due to P. gingivalis inoculation and pregnancy in an in vivo rat model of periodontal disease. A metagenomic sequencing analysis targeting seven of the 16S rRNA gene variable regions was performed for oral samples collected at the following time points: baseline control (week 0), P. gingivalis inoculated (week 11), P. gingivalis inoculated and pregnant rat at necropsy (week 16). A second set of animals were also sampled to generate a sham-inoculated (week 11) control group. We found that the rat oral microbiome profiles were more similar to that of the human oral cavity compared to previous reports targeting one or two 16S variable regions. Overall, there appears to be a relatively stable core microbiome in the oral cavity. As expected, P. gingivalis induced periodontal disease resulted in oral microbiome dysbiosis. During pregnancy, some aspects of the oral microbiome shifted toward a more baseline-like profile. However, population analyses in terms of dissimilarity measures and especially metagenomic based predictions of select characteristics such as cell morphology, oxygen requirement, and major metabolite synthesis showed that pregnancy did not restore the composition of the oral microbiome. Rather, a uniquely altered oral microbiome composition was observed in pregnant rats with pre-established periodontal disease.

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The MAIT conundrum – how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues

Cited by 21 publications

References 72 publications

Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions

Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions

MAIT cell-directed therapy of Mycobacterium tuberculosis infection

A Uniquely Altered Oral Microbiome Composition Was Observed in Pregnant Rats With Porphyromonas gingivalis Induced Periodontal Disease

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