Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis

Ardain, Amanda; Domingo-Gonzalez, Racquel; Das, Shibali; Kazer, Samuel W.; Howard, Nicole; Singh, Abhijeet; Ahmed, Mushtaq; Nhamoyebonde, Shepherd; Rangel-Moreno, Javier; Ogongo, Paul; Lu, Lan; Ramsuran, Duran; García-Hernández, María de la Luz; Ulland, Tyler K.; Darby, Matthew; Park, Eugene; Karim, Farina; Melocchi, Laura; Madansein, Rajhmun; Dullabh, Kaylesh J; Dunlap, Micah; Marin, Nancy D.; Ebihara, Takashi; Ndung’u, Thumbi; Kaushal, Deepak; Pym, Alexander S.; Kolls, Jay K.; Steyn, Adrie J. C.; Zúñiga, Joaquı́n; Horsnell, William; Yokoyama, Wayne M.; Shalek, Alex K.; Kløverpris, Henrik N.; Colonna, Marco; Leslie, Alasdair; Khader, Shabaana A.

doi:10.1038/s41586-019-1276-2

Cited by 150 publications

(216 citation statements)

References 30 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…Larger cohorts studied by advanced multiparametric technologies might help to resolve the cell heterogeneity, especially present in LTBI, found in our as well as in previous studies (69). High-dimensional cytometry analyses have been already harnessed to explore cells from differently exposed Mtb adolescents uncovering new cell subsets, including those expressing CD16+ and other populations defined as NK cells, CD27-CD8+ αβ T cells, B cells (27), and ILC3 (28).…”

Section: Discussionmentioning

confidence: 57%

“…However, it remains understudied which other cell subsets recognizing Mtb antigens may be involved in the overall response. Recent evidence for example has highlighted a role for NK cells (27) as well as ILC3 (28) in protective immunity to TB. In this study, we first validated the recognition of several recently identified Mtb antigens by multicomponent cytokine signatures in an independent cohort of LTBI and TB patients.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

et al. 2020

View full text Add to dashboard Cite

LTBI, while CD14+ TNF-α+ myeloid-like clusters were mostly abundant in adolescent LTBI. Our findings, although limited to a small cohort, stress the importance of assessing broader immune responses than IFN-γ alone in Mtb antigen discovery as well as the importance of screening individuals of different age groups. In addition, our results provide proof of concept showing how unbiased multidimensional multiparametric cell subset analysis can identify unanticipated blood cell subsets that could play a role in the immune response against Mtb.

show abstract

Section: Discussionmentioning

confidence: 57%

mentioning

confidence: 99%

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

et al. 2020

View full text Add to dashboard Cite

show abstract

“…81 ILC3s are in fact the major producers of IL-22 in the lung, 82,83 and consequently are probably important for tissue repair following viral infection. 88 Various ILC3 knock-out mouse models display reduced control of early bacteraemia, which could be restored by adoptive transfer of purified ILCs. 84 IL-22-producing ILC3s are also important for clearance of bacterial infections, such as S. pneumoniae.…”

Section: Ilc3smentioning

confidence: 99%

“…As with many of the examples cited above, timing is probably a key factor in their importance, as ILCs are the earliest responders to infection and appear to help orchestrate the subsequent immune response. 88 Various ILC3 knock-out mouse models display reduced control of early bacteraemia, which could be restored by adoptive transfer of purified ILCs.…”

Section: Ilc3smentioning

confidence: 99%

Tissue‐resident innate immunity in the lung

2019

Self Cite

View full text Add to dashboard Cite

The lung is a unique organ that must protect against inhaled pathogens and toxins, without mounting a disproportionate response against harmless particulate matter and without compromising its vital function. Tissue-resident immune cells within the lung provide local immunity and protection from infection but are also responsible for causing disease when dysregulated. There is a growing appreciation of the importance of tissue-resident memory T cells to lung immunity, but non-recirculating, tissue-resident, innate immune cells also exist. These cells provide the first line of defence against pulmonary infection and are essential for co-ordinating the subsequent adaptive response. In this review, we discuss the main lung-resident innate immune subsets and their functions in common pulmonary diseases, such as influenza, bacterial pneumonia, asthma and inflammatory disorders.

show abstract

“…Rapid early IL-17A production is known to be critical for protective immune responses in different settings of lung immunity [1], [35]. To better understand the early events unfolding in the lung during N. brasiliensis infection, we performed a Nanostring gene expression array using a myeloid immunity panel (700 genes).…”

Section: Il-17a Leads To a Downregulation Of Early Ifng During Nipposmentioning

confidence: 99%

IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection

Ajendra

Chenery

Parkinson

et al. 2019

Preprint

View full text Add to dashboard Cite

Nippostrongylus brasiliensis is a well-defined model of type 2 immunity but the early lungmigrating phase is dominated by innate IL-17A production and neutrophilia. While the importance of IL-17A is well established during microbial infections, its contribution to type 2 immunity is poorly understood. Using N. brasiliensis infection we show that Il17a-KO mice 40 exhibited an impaired type 2 immune response correlating with increased worm burden.Neutrophil depletion and reconstitution studies demonstrated that neutrophils contributed to the subsequent eosinophilia but were not responsible for the ability of IL-17A to promote type 2 cytokine responses. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased IFNγ signature in the Il17a-KO mice confirmed by enhanced IFNγ 45 protein production. Depletion of early IFNγ restored type 2 immune responses in the Il17a-KO

show abstract

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis

Cited by 150 publications

References 30 publications

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

Tissue‐resident innate immunity in the lung

IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection

Contact Info

Product

Resources

About