Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4 T cells, specific antibodies are reported along with features of lung macrophages.
View Article and Find Full Text PDFMass cytometry, or cytometry by time-of-flight (the basis for Fluidigm CyTOF technology), is a system for single-cell detection using antibodies tagged with metal probes. Without the need for compensation, the highly parametric Helios™ mass cytometer has a detection range of 135 distinct mass channels (75-209 Da). Optimized for mass cytometry, the Maxpar Direct™ Immune Profiling Assay™ is a dry, metal-tagged antibody cocktail for immunophenotyping 37 immune cell populations found in human peripheral blood in a single tube.
View Article and Find Full Text PDFSARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis.
View Article and Find Full Text PDFRegulation of proinflammatory cytokine expression is critical in the face of single-stranded RNA (ssRNA) virus infections. Many viruses, including coronavirus and influenza virus, wreak havoc on the control of cytokine expression, leading to the formation of detrimental cytokine storms. Understanding the regulation and interplay between inflammatory cytokines is critical to the identification of targets involved in controlling the induction of cytokine expression.
View Article and Find Full Text PDFJ Interferon Cytokine Res
August 2019
Interleukin (IL)-27 is a promising anti-cancer cytokine with therapeutic potential. Exhibiting overlapping properties with type I and II interferons (IFNs), IL-27 impacts cancer cell viability and immune cell activity. Known to modulate toll-like receptor (TLR) expression, we investigated whether IL-27 affected TLR-mediated death in cancer cells.
View Article and Find Full Text PDFImmune activation may underlie the pathogenesis of irritable bowel syndrome (IBS), but the evidence is conflicting. We examined whether peripheral CD4+ T-cells from IBS patients demonstrated immune activation and changes in cytokine production. To gain mechanistic insight, we examined whether immune activation correlated with psychological stress and changing symptoms over time.
View Article and Find Full Text PDFUpon repeated exposure to endotoxin or lipopolysaccharide (LPS), myeloid cells enter a refractory state called endotoxin tolerance as a homeostatic mechanism. In innate immune cells, LPS is recognized by co-receptors Toll-like receptor 4 (TLR4) and CD-14 to initiate an inflammatory response for subsequent cytokine production. One such cytokine, interleukin (IL)-27, is produced by myeloid cells in response to bacterial infection.
View Article and Find Full Text PDFInterleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27.
View Article and Find Full Text PDFFront Immunol
September 2017
Toll-like receptor (TLR)-7 is an endosomal innate immune sensor capable of detecting single-stranded ribonucleic acid. TLR7-mediated induction of type I interferon and other inflammatory cytokine production is important in antiviral immune responses. Furthermore, altered TLR7 expression levels are implicated in various autoimmune disorders, indicating a key role for this receptor in modulating inflammation.
View Article and Find Full Text PDFIL-27 bridges innate and adaptive immunity by modulating cytokine production from myeloid cells and regulating Th cell differentiation. During bacterial infection, TLR4 triggering by LPS induces IL-27 production by monocytes and macrophages. We have previously shown that IL-27 can prime monocytes for LPS responsiveness by enhancing TLR4 expression and intracellular signaling.
View Article and Find Full Text PDFThe inflammasome is a multimeric protein complex required for interleukin (IL)-1β production. Upon lipopolysaccharide (LPS) triggering of toll-like receptor (TLR)-4 and subsequent ATP signaling, the NOD-like receptor containing-pyrin domain 3 (NLRP3) inflammasome is activated to cleave pro-caspase-1 into caspase-1, allowing the secretion of IL-1β. IL-1β is known to function with IL-23 in the regulation of IL-17-producing CD4(+) T cells, Th17 cells, in adaptive immunity.
View Article and Find Full Text PDFJ Interferon Cytokine Res
December 2015
Proinflammatory cytokines are produced by macrophages and dendritic cells (DCs) after infection to stimulate T helper (Th) cells, linking innate and adaptive immunity. Virus infections can deregulate the proinflammatory cytokine response like tumor necrosis factor-α and interleukin (IL)-2, making the host more susceptible to secondary bacterial infections. Studies using various viruses such as lymphocytic choriomeningitis virus, influenza A virus, and human immunodeficiency virus have revealed several intriguing mechanisms that account for the increased susceptibility to several prevalent bacterial infections.
View Article and Find Full Text PDFBackground: Severe and fatal malaria are associated with dysregulated host inflammatory responses to infection. Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein implicated in regulating immune responses. Expression and function of CHI3L1 in malaria infection were investigated.
View Article and Find Full Text PDFThe interleukin (IL)-12 family cytokine, IL-27 has been implicated in the pathogenesis of many autoimmune inflammatory disorders, including rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn's disease, and ulcerative colitis. Discovered in 2002, IL-27 has been primarily described as an anti-inflammatory cytokine with regulatory roles in multiple sclerosis and experimental autoimmune encephalitis. However, recent studies have demonstrated a pro-inflammatory function of IL-27 in both the adaptive and innate immune responses.
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