scholarly journals Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2

2020 ◽  
Vol 6 (9) ◽  
pp. eaay9269
Author(s):  
Yong Fu ◽  
Yan Ding ◽  
Qinghui Wang ◽  
Feng Zhu ◽  
Yulong Tan ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Blood Stage ◽  
Innate Immune Responses ◽  
Malaria Parasites ◽  
Monocyte Chemoattractant Protein 1 ◽  
Blood Stage Malaria

Malaria parasites suppress host immune responses to facilitate their survival, but the underlying mechanism remains elusive. Here, we found that blood-stage malaria parasites predominantly induced CD4+Foxp3+CD25+ regulatory T cells to release soluble fibrinogen-like protein 2 (sFGL2), which substantially enhanced the infection. This was attributed to the capacity of sFGL2 to inhibit macrophages from releasing monocyte chemoattractant protein-1 (MCP-1) and to sequentially reduce the recruitment of natural killer/natural killer T cells to the spleen and the production of interferon-γ. sFGL2 inhibited c-Jun N-terminal kinase phosphorylation in the Toll-like receptor 2 signaling pathway of macrophages dependent on FcγRIIB receptor to release MCP-1. Notably, sFGL2 were markedly elevated in the sera of patients with malaria, and recombinant FGL2 substantially suppressed Plasmodium falciparum from inducing macrophages to release MCP-1. Therefore, we highlight a previously unrecognized immune suppression strategy of malaria parasites and uncover the fundamental mechanism of sFGL2 to suppress host innate immune responses.

scholarly journals Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
S. Abigail Smith ◽  
Phillip M. Murray ◽  
Praveen Kumar Amancha ◽  
Cassie G. Ackerley ◽  
Yi-Juan Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Marginal Zone ◽  
Ex Vivo ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Hiv Replication ◽  
Hiv 1

AbstractOur understanding of innate immune responses in human rectal mucosal tissues (RM) and their contributions to promoting or restricting HIV transmission is limited. We defined the RM composition of innate and innate-like cell subsets, including plasmacytoid dendritic cells; CD1c + myeloid DCs; neutrophils; macrophages; natural killer cells (NK); Marginal Zone-like B cells (MZB); γδ T cells; and mucosal-associated invariant T cells in RM from 69 HIV-negative men by flow cytometry. Associations between these cell subsets and HIV-1 replication in ex vivo RM explant challenge experiments revealed an inverse correlation between RM-NK and p24 production, in contrast to a positive association between RM-MZB and HIV replication. Comparison of RM and blood-derived MZB and NK illustrated qualitative and quantitative differences between tissue compartments. Additionally, 22 soluble molecules were measured in a subset of explant cultures (n = 26). Higher production of IL-17A, IFN-γ, IL-10, IP-10, GM-CSF, sFasL, Granzyme A, Granzyme B, Granulysin, and Perforin following infection positively correlated with HIV replication. These data show novel associations between MZB and NK cells and p24 production in RM and underscore the importance of inflammatory cytokines in mucosal HIV infection, demonstrating the likely critical role these innate immune responses play in early mucosal HIV replication in humans.

scholarly journals The Absence of Hck, Fgr, and Lyn Tyrosine Kinases Augments Lung Innate Immune Responses to Pneumocystis murina

2009 ◽  
Vol 77 (5) ◽  
pp. 1790-1797 ◽  
Author(s):  
Michael P. Nelson ◽  
Allison E. Metz ◽  
Shaoguang Li ◽  
Clifford A. Lowell ◽  
Chad Steele
Keyword(s):  
Immune Responses ◽  
Alveolar Macrophages ◽  
Tyrosine Kinases ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Independent Manner ◽  
Intratracheal Administration ◽  
Monocyte Chemoattractant Protein 1 ◽  
Immunoglobulin Receptor

ABSTRACT Src family tyrosine kinases (SFKs) phosphorylate immunotyrosine activation motifs in the cytoplasmic tail of multiple immunoreceptors, leading to the initiation of cellular effector functions, such as phagocytosis, reactive oxygen species production, and cytokine production. SFKs also play important roles in regulating these responses through the activation of immunotyrosine inhibitory motif-containing inhibitory receptors. As myeloid cells preferentially express the SFKs Hck, Fgr, and Lyn, we questioned the role of these kinases in innate immune responses to Pneumocystis murina. Increased phosphorylation of Hck was readily detectable in alveolar macrophages after stimulation with P. murina. We further observed decreased phosphorylation of Lyn on its C-terminal inhibitory tyrosine in P. murina-stimulated alveolar macrophages, indicating that SFKs were activated in alveolar macrophages in response to P. murina. Mice deficient in Hck, Fgr, and Lyn exhibited augmented clearance 3 and 7 days after intratracheal administration of P. murina, which correlated with elevated levels of interleukin 1β (IL-1β), IL-6, CXCL1/KC, CCL2/monocyte chemoattractant protein 1, and granulocyte colony-stimulating factor in lung homogenates and a dramatic increase in macrophage and neutrophil recruitment. Augmented P. murina clearance was also observed in Lyn−/− mice 3 days postchallenge, although the level was less than that observed in Hck−/− Fgr−/− Lyn−/− mice. A correlate to augmented clearance of P. murina in Hck−/− Fgr−/− Lyn−/− mice was a greater ability of alveolar macrophages from these mice to kill P. murina in vitro, suggesting that SFKs regulate the alveolar macrophage effector function against P. murina. Mice deficient in paired immunoglobulin receptor B (PIR-B), an inhibitory receptor activated by SFKs, did not exhibit enhanced inflammatory responsiveness to or clearance of P. murina. Our results suggest that SFKs regulate innate lung responses to P. murina in a PIR-B-independent manner.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

scholarly journals Polysaccharides derived from Yamoa™ (Funtumia elastica) prime γδ T cells in vitro and enhance innate immune responses in vivo

2009 ◽  
Vol 9 (11) ◽  
pp. 1313-1322 ◽  
Author(s):  
Jill C. Graff ◽  
Emily M. Kimmel ◽  
Brett Freedman ◽  
Igor A. Schepetkin ◽  
Jeff Holderness ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Innate Immune ◽  
Innate Immune Responses
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