In:
The Journal of Immunology, The American Association of Immunologists, Vol. 206, No. 1_Supplement ( 2021-05-01), p. 96.03-96.03
Abstract:
Neutrophils are protective against early Mycobacterium tuberculosis (Mtb) infection, but overactive neutrophil response is often associated with chronic lung inflammation, tissue damage and compromised T-cell immunity, implying potential immunosuppression by neutrophils in Mtb infection. To test this, we examined the effect of peripheral blood neutrophils on the immune responses of T-cells from the peripheral blood mononuclear cells (PBMC) of persons with latent tuberculosis infection. Co-cultures of PBMC with autologous neutrophils at different ratios inhibited Mtb-stimulated T-cell proliferation and cytokines IFN-γ, IL-17 and IL-10 production dose dependently without affecting cell viability as determined by resazurin assay for cell metabolism and annexin V/PI staining for cell death. Neutralization of IL-10 and TGF-β failed to rescue neutrophil suppression of T-cell IFN-γ production. Neutrophils suppressed IFN-γ mRNA expression as determined by qPCR. Neutrophils inhibited purified T-cells stimulated with immobilized anti-CD3 and anti-CD28 mAbs, suggesting direct effect on T-cells without the involvement of antigen presenting cells. Trans-well study showed that cell-cell contact is required for this suppression. Further assessment of granulocyte derived suppressor cell phenotype and blocking the interaction between immune checkpoint molecules, PD-1 and PD-L1, refuted their roles in suppression of T-cells responses in Mtb infection. Together, these data suggest that neutrophils suppress T-cell immune responses by direct cell-cell contact mechanism and identification of molecular details of such suppression will shed new insights into the pathogenesis of tuberculosis and other infectious diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.206.Supp.96.03
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2021
detail.hit.zdb_id:
1475085-5
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