T cell expression of MyD88 is required for resistance to<i>Toxoplasma gondii</i>

LaRosa, David F.; Stumhofer, Jason S.; Gelman, Andrew E.; Rahman, Adeeb; Taylor, Daniel D.; Hunter, Christopher A.; Turka, Laurence A.

doi:10.1073/pnas.0706663105

Cited by 101 publications

(104 citation statements)

References 47 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Neutrophils participate in host response to T. gondii but play a limited role in survival of WT mice infected with the parasite (30-32). Instead, IFN-γ from NK and T cells predetermined susceptibility vs. resistance to the parasite (12,16,33). The dominance of neutrophils in IFN-γ production observed in T. gondii-infected TLR11 −/− mice prompted us to investigate their physiological importance.…”

Section: Percetage Of Ifn-+ Cellsmentioning

confidence: 99%

TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens

Sturge¹,

Benson²,

Raetz³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

IFN-γ is a major cytokine that is critical for host resistance to a broad range of intracellular pathogens. Production of IFN-γ by natural killer and T cells is initiated by the recognition of pathogens by Toll-like receptors (TLRs). In an experimental model of toxoplasmosis, we have identified the presence of a nonlymphoid source of IFN-γ that was particularly evident in the absence of TLR-mediated recognition of Toxoplasma gondii . Genetically altered mice lacking all lymphoid cells due to deficiencies in Recombination Activating Gene 2 and IL-2Rγ c genes also produced IFN-γ in response to the protozoan parasite. Flow-cytometry and morphological examinations of non-NK/non-T IFN-γ + cells identified neutrophils as the cell type capable of producing IFN-γ. Selective elimination of neutrophils in TLR11 −/− mice infected with the parasite resulted in acute susceptibility similar to that observed in IFN-γ–deficient mice. Similarly, Salmonella typhimurium infection of TLR-deficient mice induces the appearance of IFN-γ + neutrophils. Thus, neutrophils are a crucial source for IFN-γ that is required for TLR-independent host protection against intracellular pathogens.

show abstract

Section: Percetage Of Ifn-+ Cellsmentioning

confidence: 99%

TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens

Sturge¹,

Benson²,

Raetz³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

show abstract

“…TRAF6 is an E3 ubiquitin ligase and catalyzes K63 polyubiquitination of TAK1, which is required for IKK activation and is known to directly regulate ubiquitination and activation of AKT and mTORC1 as well as TGF-β (14)(15)(16)(17). Interestingly, CD4 or CD8 T cells lacking MyD88 exhibit reduced expansion and impaired survival in vivo (4)(5)(6)(7)(8)(9)(10). IRAK4 has been reported to be recruited to T cell lipid rafts, where it associates with ZAP70 and participates in protein kinase C activation (18).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies highlight an indispensable role for MyD88 signaling in primary T cells (4)(5)(6)(7)(8)(9)(10). The engagement of IL-1 receptor family members as well as TLRs (except TLR3) recruits the adapter protein MyD88, which in turn brings in an IL-1 receptor-associated kinase 4 (IRAK4), resulting in autophosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of IRAK1/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies

Li¹,

Younger²,

Gartenhaus³

et al. 2015

J. Clin. Invest.

View full text Add to dashboard Cite

“…Although it is not entirely clear how innate MyD88-dependent signaling regulates the activation of T-cell responses, it has been suggested that MyD88 expression in antigen-presenting cells (APCs), including dendritic cells (DCs), plays a key role in the activation of T-cell responses (2,15,27,39). Additionally, very recent studies have revealed an important role of MyD88 expression in T cells in regulating T-cell activation and pathogenesis in response to model antigens or parasites (11,26). However, it is not known whether MyD88 expression in T cells plays a similar role in the activation of T cells and regulation of pathogenesis in response to a virus.…”

mentioning

confidence: 99%