Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia

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Patients with AIDS, cancer or immune suppressive treatments are vulnerable to infection with invasive fungi. We have found that even when helper CD4 T cells are profoundly reduced in a mouse model that mimics this defect in AIDS, other remaining T cells are capable of mounting vaccine immunity against a deadly fungal infection, and they do so by producing the powerful, soluble product, IL-17. It has been widely believed that the activation and instruction of such cells, called Tc17 cells, is governed by another population of immune cells in the body, but we have found here that pathways within these Tc17 cells themselves mediate their activation and ability to produce the IL-17 needed for resistance to infection. We have also identified elements of the circuitry controlling this pathway—elements called MyD88, Akt1 and mTOR—and found that they control the production of IL-17 and not other products such as IFN-γ often produced by these cells. Further, we determined that this circuitry controls the development of Tc17 cells by regulating their ability to divide and expand. Thus, in a mouse model of vaccination against lethal fungal pneumonia caused by Blastomyces dermatitidis, we uncovered an important cellular arsenal that can be recruited to bolster resistance against a fungal infection, and identified novel ways in which the cells develop and expand into potent killers of fungi.

Vyšlo v časopise: Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005161
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005161

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