Modulation of gut immune response by probiotic fermented milk consumption to control IgE in a respiratory allergy model

2021 ◽  
Vol 12 (2) ◽  
pp. 175-186
Author(s):  
E. Velez ◽  
I. Novotny-Nuñez ◽  
S. Correa ◽  
G. Perdigón ◽  
C. Maldonado-Galdeano
Keyword(s):  
Fermented Milk ◽  
Respiratory Allergy ◽  
Allergic Response ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Specific Immunoglobulin ◽  
Specific Igg ◽  
Ifn Γ ◽  
Lower Count ◽  
Pro Inflammatory Cytokines

Allergies are a world increasing health issue and most treatments are oriented to alleviate symptoms. Probiotics have several health benefits including the improvement of the immune system. In previous work we found that consumption of commercial probiotic fermented milk (PFM) significantly reduced specific-immunoglobulin (Ig) E in serum and lungs by increasing specific-IgG and controlled allergic response to ovalbumin (OVA) in an adult mouse respiratory allergy model. Here we continued our study determining the mechanism triggered in the gut by the PFM ingestion that influenced the results previously reported. Five groups of BALB/c mice were assessed: normal-control, basal (drinks PFM five days without OVA sensitisation), sensitisation-control (no PFM intake), previous and continuous-PFM administration. Allergen administration: 3 OVA injections (1% in PBS) followed by aerosols exposure for 7 days. We determined total secretory-IgA and cytokines in small intestine (SI) fluid; CD11b+, CD103+, IgA+ cells and cytokine producing cells in SI tissue. In lungs we analysed co-expression of CD4/interferon (IFN)-γ or CD4/interleukin (IL)-10, IgE+ cells and IL-12 production. Results: continuous intake of PFM increased the expression of CD103 marker and decreased CD11b and pro-inflammatory cytokines. Coexpression of CD4/IFN-γ was confirmed in lungs of animals that consumed PFM continuously. This group had a lower count of IgE+ cells and a higher concentration of IL-12. The consumption of PFM reinforces the mucosal barrier by increasing IgA+ cells and induces signalling from the intestine to the lungs by increasing the expression of CD103+ dendritic cells related to regulatory mechanisms. The results found in this work together with those previously reported demonstrated that the intake of PFM induces a clear balance towards the Th1 response, preventing the Th2 allergic response by controlling the previously reported IgE level. According to our model, the intake of PFM could be a good strategy to alleviate the development of allergies.

Respiratory allergy control by probiotic fermented milk intake: a mouse model from weaning to maturity

2020 ◽  
Vol 11 (8) ◽  
pp. 767-778
Author(s):  
E.M.M. Velez ◽  
R. Weill ◽  
M.C. Maldonado-Galdeano ◽  
G. Perdigón
Keyword(s):  
Immune Cells ◽  
Fermented Milk ◽  
Specific Ige ◽  
Treg Cells ◽  
Respiratory Allergy ◽  
Secretory Iga ◽  
Monocyte Chemoattractant Protein 1 ◽  
Adult Mice ◽  
Ifn Γ ◽  
The Impact

This study is based on our previous research showing that commercial probiotic fermented milk (PFM) intake mitigates respiratory allergy development to ovalbumin (OVA) in adult mice (6-weeks old) increasing specific immunoglobulin (Ig)G2a and interferon (IFN)-γ rather than IgE. The aim was to determine if PFM exerts a protective effect when an allergy model is induced 5 days after weaning and whether the mechanisms involved are similar to those previously reported. Before inducing allergy, a group of 21-day old BALB/c mice received PFM for 10 days to analyse the impact on intestinal epithelial cells (IECs) activation. Two more groups received PFM for 5 days and were sensitised with OVA; only one group continued taking PFM until the end of the experiment. Sensitisation scheme: 3 OVA injections 1% in phosphate buffered saline (PBS) plus 7 days OVA aerosol exposure and re-stimulus 15 days later. The contents of specific- IgE, IgG, total-secretory-IgA and Th1/Th2 balance in serum, bronchoalveolar lavage (BAL) and gut were measured at 7 and 15 days post-sensitisation (dPS) and 2 days post-re-stimulus (2dPR). Treg cells in lungs were also quantified. Results were compared with normal and sensitised controls. PFM induced mild activation of IECs increasing monocyte chemoattractant protein-1 (MCP-1 or CCL2) and interleukin (IL)-6 production. In sensitised mice, PFM controlled the response inducing IgG rather than IgE at 7 and 15-dPS and 2dPR (60 days old). Th1-balance (IFN-γ) was favoured by PFM in lungs at 7 dPS with low levels of IL-10 released to regulate the response. Total-S-IgA increased in lungs and gut; however, PFM intake did not affect Treg cells in lungs. PFM maintains controlled stimulation of the immune cells involved in Th1 response, favouring IgG at the respiratory mucosal site. Although the effect was not as strong as that reported previously, PFM promoted maturation and activation of gut immune cells preserving intestinal homeostasis and lung immune response.

scholarly journals Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice

2015 ◽  
Vol 114 (4) ◽  
pp. 566-576 ◽  
Author(s):  
Eva M. M. Velez ◽  
Carolina Maldonado Galdeano ◽  
Esteban Carmuega ◽  
Ricardo Weill ◽  
María E. Bibas Bonet ◽  
...  
Keyword(s):  
Lavage Fluid ◽  
Fermented Milk ◽  
Specific Ige ◽  
Interferon Γ ◽  
Secretory Iga ◽  
Th2 Cells ◽  
Potential Efficacy ◽  
Ifn Γ ◽  
Underlying Mechanisms ◽  
Micro Organisms

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisation process. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treating allergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed with PFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-γ (IFN-γ), IL-4, IL-10 and total secretory IgA (S-IgA) were measured in the supernatants of macerated lungs or in the BALF. The levels of IgA+, CD4+and CD8+T lymphocytes and F4/80+cells were measured in the lungs by immunofluorescence. Inducible CD4+/CD25/Foxp3+regulatory T (Treg) cells were evaluated in the lungs. PFM shifted the T helper (Th)2 profile response towards a Th1 response that led to the production of IgG instead of IgE, with increasing levels of IL-10 and IFN-γ that play an important role in immunomodulation exerted by PFM administration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels of anti-OVA-specific IgG and total S-IgA. PFM did not influence Tregcells in treated mice. Consumption of PFM could be a promising strategy in the amelioration of airway allergies, considering that the effect is mediated by the production of IgG through the activation of Th1 instead of the direct activation of Th2 cells to produce IgE.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

scholarly journals Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Hacat Cells ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mapk Signaling Pathways ◽  
Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

scholarly journals Ecklonia cava Attenuates PM2.5-Induced Cognitive Decline through Mitochondrial Activation and Anti-Inflammatory Effect

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 131
Author(s):  
Seon Kyeong Park ◽  
Jin Yong Kang ◽  
Jong Min Kim ◽  
Hyun-Jin Kim ◽  
Ho Jin Heo
Keyword(s):  
Water Extract ◽  
Ecklonia Cava ◽  
Mitochondrial Activity ◽  
Memory Decline ◽  
Mitochondria Membrane Potential ◽  
Mitochondrial Ros ◽  
Ifn Γ ◽  
Related Proteins ◽  
The Brain ◽  
Pro Inflammatory Cytokines

To evaluate the effects of Ecklonia cava (E. cava) on ambient-pollution-induced neurotoxicity, we used a mouse model exposed to particulate matter smaller than 2.5 µm in aerodynamic diameter (PM2.5). The intake of water extract from E. cava (WEE) effectively prevented the learning and memory decline. After a behavioral test, the toll-like receptor (TLR)-4-initiated inflammatory response was confirmed by PM2.5 exposure in the lung and brain tissues, and the WEE was regulated through the inhibition of nuclear factor-kappa B (NF-κB)/inflammasome formation signaling pathway and pro-inflammatory cytokines (IL-6 and IFN-γ). The WEE also effectively improved the PM2.5-induced oxidative damage of the lungs and brain through the inhibition of malondialdehyde (MDA) production and the activation of mitochondrial activity (mitochondrial ROS content, mitochondria membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic molecules). In particular, the WEE regulated the cognition-related proteins (a decreased amyloid precursor protein (APP) and p-Tau, and an increased brain-derived neurotrophic factor (BDNF)) associated with PM2.5-induced cognitive dysfunction. Additionally, the WEE prevented the inactivation of acetylcholine (ACh) synthesis and release as a neurotransmitter by regulating the acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), and ACh receptor (AChR)-α3 in the brain tissue. The bioactive compounds of the WEE were detected as the polysaccharide (average Mw; 160.13 kDa) and phenolic compounds including 2′-phloroeckol.

Depletion of gut secretory immunoglobulin A coated Lactobacillus reuteri is associated with gestational diabetes mellitus-related intestinal mucosal barrier damage

2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lactobacillus Reuteri ◽  
Immunoglobulin A ◽  
Mucosal Damage ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Secretory Immunoglobulin

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.

scholarly journals Seropositivity to Nucleoprotein to detect SARS-CoV-2 infections: a tool to detect breakthrough infections after COVID-19 vaccination

2021 ◽  
Author(s):  
Lotus Leonie van den Hoogen ◽  
Gaby Smits ◽  
Cheyenne CE van Hagen ◽  
Denise Wong ◽  
Eric RA Vos ◽  
...  
Keyword(s):  
Immune Response ◽  
Primary Infection ◽  
Spike Protein ◽  
Multiplex Immunoassay ◽  
Specific Immunoglobulin ◽  
Vaccination History ◽  
Specific Igg ◽  
Exposure History ◽  
Asymptomatic Individuals ◽  
Roll Out

Background With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Methods Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). Results The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naïve participants. Conclusions Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

scholarly journals The effect of Kefir on The Immune Response of Healthy Volunteers In Vitro

2017 ◽  
Vol 3 (2) ◽  
pp. 28
Author(s):  
Desie Dwi Wisudanti
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Fermented Milk ◽  
Bioactive Components ◽  
Ifn Γ

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.

scholarly journals Differential Glycosylation Between Recombinant Factor VIII Produced in Baby Hamster Kidney and Chinese Hamster Ovary Cells Confers Differences in Immunogenicity in a Humanized Hemophilia Α Mouse Model

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 326-326 ◽  
Author(s):  
Jesse Lai ◽  
Laura L Swystun ◽  
Dominique Cartier ◽  
Cunjie Zhang ◽  
Kate Nesbitt ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Factor Viii ◽  
Research Funding ◽  
Clinical Evidence ◽  
Lectin Binding ◽  
Chinese Hamster ◽  
Specific Igg ◽  
Ifn Γ ◽  
High Mannose

Abstract Introduction The formation of factor VIII (FVIII)- neutralizing antibodies is the most critical complication in the treatment of hemophilia A (HA). Recent clinical evidence suggests that recombinant FVIII (rFVIII) produced in baby hamster kidney (BHK-rFVIII) cells is more immunogenic than that produced in Chinese hamster ovary (CHO-rFVIII) cells. This difference in FVIII immunogenicity may be attributed to differences in protein glycosylation, which can impact the removal of FVIII from circulation through mechanisms leading to clearance and antigen presentation. Here, we document significant differences among the 25 potential N-linked glycans between these products, and we provide in vivo animal model-based evidence that supports these clinical observations. Methods Factor VIII lectin binding was assessed by ELISA to detect exposed glycans. Commercially-available rFVIII products were adsorbed at 1 ug/mL and specific glycan moieties were detected using a panel of biotinylated lectins and HRP-conjugated streptavidin. Confirmation of differences and determination of N-linked glycan structures was conducted by LC-MS/MS. Eight to 12 week old transgenic C57BL/6 HA mice were used in these studies. This model contains a murine f8 exon 16 KO and additionally harbors a human F8 transgene with a R593C point mutation. While these mice have undetectable plasma levels of human FVIII antigen and activity, they are tolerant to intravenously infused human rFVIII. Clearance was assessed following a 6 IU (~240 IU/kg) infusion of each rFVIII product, and FVIII activity was measured by chromogenic assay and normalized to a 5-minute time point. The number of interferon (IFN)-γ secreting splenocytes from rFVIII-primed naïve mice was determined by ELISPOT. FVIII immune responses were elicited by subcutaneous infusion (6 IU twice-weekly for 2 weeks) and adjuvant-coupled intravenous infusion (1 ug lipopolysacharride with the first infusion as described above) with either rFVIII product. Week 5 plasma samples were assessed for FVIII-specific IgG by ELISA, and FVIII inhibitors by one-stage clotting assay. Results Lectin binding showed that rFVIII produced in BHK cell lines exhibit lower proportions of high-mannose glycans (p<0.01), and greater levels of sialic acid capping (p<0.01) and fucosylated glycans (p<0.01). Mass spectra confirmed higher levels of sialic acid and identified two additional N-linked sites bearing high mannose glycans on CHO-rFVIII. In this mouse model we observed that BHK-rFVIII had a circulating half-life of 6.06 hours compared to the 10.01 hour half-life of CHO-rFVIII (p<0.0001). The immunogenicity of the BHK- and CHO-rFVIII products was next evaluated in vivo. In mice primed with a single 6 IU dose of BHK-rFVIII, we identified a higher proportion of FVIII-specific IFN-γ secreting splenocytes after seven days. Furthermore, long-term studies showed that 100% of mice subcutaneously exposed to BHK-rFVIII developed anti-FVIII IgG compared to the 47% that received CHO-rFVIII (p<0.01). Coincidently, when FVIII inhibitors were measured, we observed an incidence of 100% vs 37% (p<0.01), respectively. While the titres of FVIII-specific IgG were higher in mice exposed to BHK-rFVIII (p<0.01), there were no significant differences in the inhibitor concentrations. Similarly, we observed increased titres of FVIII-specific IgG in mice exposed intravenously (1 ug LPS with the first infusion) to BHK-rFVIII compared to CHO-rFVIII. However, there were no differences in the incidence of FVIII-specific IgG, nor in the incidence and concentration of inhibitors between the intravenously-infused mice. Conclusions Our results demonstrate that BHK-rFVIII exhibits altered pharmacokinetic and immunogenic properties compared to CHO-rFVIII in humanized hemophilia A mice. The observed early increase in the proportion FVIII-specific IFN-γ producing cells in the spleen suggests an intrinsic immunogenic element of BHK-rFVIII. Similarly, the substantially increased immunogenicity of BHK-rFVIII in mice when treated subcutaneously complements the previously-reported clinical evidence. These differences may be attributed to the significant disparities in N-linked glycosylation, most notably high mannose and sialic acid containing glycans. Additional studies are underway to directly address the role of the these specific glycans and their potential impact on immunogenicity of rFVIII. Disclosures Lillicrap: Octapharma: Research Funding; Baxalta: Research Funding; Biogen-Idec: Research Funding; Bayer: Research Funding.

scholarly journals Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles

2021 ◽  
Vol 12 ◽  
Author(s):  
Eduardo S. Felismino ◽  
Juliana M. B. Santos ◽  
Marcelo Rossi ◽  
Carlos A. F. Santos ◽  
Edison L. Durigon ◽  
...  
Keyword(s):  
Older Adults ◽  
T Cells ◽  
Influenza Virus ◽  
Exercise Training ◽  
Serum Levels ◽  
Specific Antibody Response ◽  
Post Vaccination ◽  
Specific Immunoglobulin ◽  
Specific Igg ◽  
Regular Practice

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups—non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)—for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p &lt; 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p &lt; 0.05) and CET (p &lt; 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p &lt; 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p &lt; 0.05 and p &lt; 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p &lt; 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p &lt; 0.05) and increased IL-10 levels post-vaccination (p &lt; 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.

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