scholarly journals Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1535
Author(s):  
Eunhan Cho ◽  
Bailey Theall ◽  
James Stampley ◽  
Joshua Granger ◽  
Neil M. Johannsen ◽  
...  

Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20–35 years—45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.

2021 ◽  
Author(s):  
Kristi J Warren ◽  
Jill A Poole ◽  
Jenea M Sweeter ◽  
Jane M DeVasure ◽  
John D Dickinson ◽  
...  

Abstract Background: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: Saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 hours after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 hours after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 in RSV-induced asthma exacerbation.


2007 ◽  
Vol 39 (Supplement) ◽  
pp. S61
Author(s):  
Richard J. Simpson ◽  
Cormac Cosgrove ◽  
Geraint D. Florida-James ◽  
Greg P. Whyte ◽  
Hanspeter Pircher ◽  
...  

2007 ◽  
Vol 103 (1) ◽  
pp. 396-401 ◽  
Author(s):  
Richard J. Simpson ◽  
Geraint D. Florida-James ◽  
Cormac Cosgrove ◽  
Greg P. Whyte ◽  
Scott Macrae ◽  
...  

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 ± 9 yr; maximal O2 uptake 62 ± 6 ml·kg−1·min−1) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise ( P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population ( P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.


2018 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Brasseit ◽  
Cheong K. C. Kwong Chung ◽  
Mario Noti ◽  
Daniel Zysset ◽  
Nina Hoheisel-Dickgreber ◽  
...  

2014 ◽  
Vol 94 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Hrvoje Valpotić ◽  
Marcela Šperanda ◽  
Ana Kovšca-Janjatović ◽  
Mislav Ðidara ◽  
Gordana Lacković ◽  
...  

Valpotić, H., Šperanda, M., Kovšca-Janjatović, A., Ðidara, M., Lacković, G., Božić, F., Habrun, B., Srečec, S., Mataušić-Pišl, M. and Valpotić, I. 2014. Levamisole stimulates proliferation of circulating and intestinal immune cell subsets, gut health and performance in weaned pigs. Can. J. Anim. Sci. 94: 43–53. With the growing knowledge of the porcine immune system and its endogenous modulation, it has been clearly stated that exogenous modulation through the use of substances able to modulate immune functions represents an important prophylactic/therapeutic approach in prevention/treatment of both stress- and F4+ and F18+ enterotoxigenic E. coli (ETEC)-induced infections accompanied weaning. The aim of this study was to evaluate the effectiveness of levamisole (LEVA; 2.5 mg kg−1 BW in 10 mL) applied per os to weaned pigs in proliferation of circulating and intestinal immune cell subsets throughout a period of 5 wk. Changes in proportion or number of peripheral blood and ileal mucosal leukocytes tested were studied either weekly by flow cytometry or at the end of the experiment (day 35) by immunohistology/histomorphometry, respectively. Pigs treated with LEVA had increased proportions of peripheral blood CD45+ lymphoid cells, CD4+ and CD8+ T cells, and CD21+ B cells (P<0.01) between days 14 and 35 following the treatment. Also, LEVA stimulated the proliferation of CD45RA+ naïve lymphoid cells in interfollicular (P<0.001) and follicular areas (P<0.05) of ileal Peyer’s patches at day 35 of the experiment. These pigs had a significantly higher (P<0.05) average body weight (19.7 vs. 17.1 kg) and weight gain at the end of experiment compared with the control pigs (for 15%). We conclude that LEVA stimulated the proliferation of circulating and intestinal lymphoid cell subsets tested and improved performance in weaned pigs, and thus, the drug may nonspecifically enhance their immunity/resistance to F4+ and F18+ ETEC strains.


2021 ◽  
Vol 12 ◽  
Author(s):  
Michelle Schmid ◽  
Helena Caria Martins ◽  
Gerhard Schratt ◽  
Julia M. Kröpfl ◽  
Christina M. Spengler

Acute exercise enhances circulating stem and precursor cells (CPCs) in the peripheral blood. The responsible mechanisms and molecular pathways, however, have not been fully identified. The aim of the present study was to investigate a pathway related to elevated levels of apoptotic peripheral blood mononuclear cells (MNCs) and their secretome. An increased uptake of miRNA126 in MNCs was suggested to lead to reduced levels of RGS16 mRNA and, in turn, an enhanced translation and secretion of CXCL12. Eighteen healthy, young men underwent two identical incremental cycling exercises of which the first served as control while the second was preceded by a 7-day-long antioxidative supplementation. Blood samples were collected at baseline (−10min) and several time points after exercise (0, 30, 90, 180, and 270min). Relative concentrations of miRNA126 in MNCs and CXCL12 levels in plasma were determined at all time points while RGS16 mRNA was assessed in MNCs at baseline and 30min after exercise. CXCL12 increased after exercise and strongly correlated with CPC numbers. MiRNA126 increased 30min and, to a lesser extent, also 180 and 270min after exercise but only with supplementation. RGS16 mRNA decreased 30min after exercise independent of the intervention. The amount of RGS16 mRNA inversely correlated with levels of miRNA126, but not with plasma CXCL12. In conclusion, even though plasma CXCL12 correlated with CPC numbers, the increase in CXCL12 cannot be explained by the increased concentration of miRNA126 and lower RGS16 mRNA in MNCs that would have allowed for an enhanced translation of CXCL12.Clinical Trial Registration: ClinicalTrials.gov, NCT03747913. Registered 20 November 2018, https://clinicaltrials.gov/ct2/show/NCT03747913.


2019 ◽  
Vol 95 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Sabrina Bianca Bennstein ◽  
Angela Riccarda Manser ◽  
Sandra Weinhold ◽  
Nadine Scherenschlich ◽  
Markus Uhrberg

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sonja Koch ◽  
Lisa Knipfer ◽  
Julia Kölle ◽  
Hooman Mirzakhani ◽  
Anna Graser ◽  
...  

Abstract Here we investigated the role of NFAT-interacting protein (NIP)-45, an Interleukin (IL)-4 inducing Transcription Factor, and its impact on the differentiation of Group 2 Innate -Lymphoid -Cells (ILC2s) in the pathogenesis of asthma. NIP45, a transcription factor regulating NFATc1 activity, mRNA was found to be induced in the Peripheral Blood mononuclear cells (PMBCs) of asthmatic pre-school children with allergies and in the peripheral blood CD4+ T cells from adult asthmatic patients. In PBMCs of asthmatic and control children, NIP45 mRNA directly correlated with NFATc1 but not with T-bet. Targeted deletion of NIP45 in mice resulted in a protective phenotype in experimental asthma with reduced airway mucus production, airway hyperresponsiveness and eosinophils. This phenotype was reversed by intranasal delivery of recombinant r-IL-33. Consistently, ILC2s and not GATA3+ CD4+ T-cells were decreased in the lungs of asthmatic NIP45−/− mice. Reduced cell number spleen ILC2s could be differentiated from NIP45−/− as compared to wild-type mice after in vivo injection of a microcircle-DNA vector expressing IL-25 and decreased cytokines and ILC2 markers in ILC2 differentiated from the bone marrow of NIP45−/− mice. NIP45 thus emerges as a new therapeutic target for the resolution of the airway pathology, down-regulation of ILC2s and mucus production in asthma.


Sign in / Sign up

Export Citation Format

Share Document