scholarly journals Cytokine responses to two common respiratory pathogens in children are dependent on interleukin-1β

2017 ◽  
Vol 3 (4) ◽  
pp. 00025-2017 ◽  
Author(s):  
Alice C-H. Chen ◽  
Yang Xi ◽  
Melanie Carroll ◽  
Helen L. Petsky ◽  
Samantha J. Gardiner ◽  
...  
Keyword(s):  
Cellular Response ◽  
Mononuclear Cells ◽  
Cell Types ◽  
Respiratory Pathogens ◽  
Peripheral Blood Mononuclear ◽  
Multiple Cell ◽  
Ifn Γ ◽  
High Concentrations ◽  
Cellular Immune ◽  
And Control

Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear.This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway.Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells.Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

scholarly journals Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

2003 ◽  
Vol 71 (6) ◽  
pp. 3165-3171 ◽  
Author(s):  
Vladimir Michailowsky ◽  
Keith Luhrs ◽  
Manoel Otávio C. Rocha ◽  
David Fouts ◽  
Ricardo T. Gazzinelli ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Chagas Disease ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Cellular Responses ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

scholarly journals Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation

2009 ◽  
Vol 77 (5) ◽  
pp. 1888-1893 ◽  
Author(s):  
Taufiqur Rahman Bhuiyan ◽  
Samuel B. Lundin ◽  
Ashraful Islam Khan ◽  
Anna Lundgren ◽  
Jason B. Harris ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Vibrio Cholerae ◽  
Mononuclear Cells ◽  
Acute Stage ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Vibrio Cholerae O1 ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-γ) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4+ T cells (CD4+ β7+), gut-homing CD8+ T cells (CD8+ β7+), and gut-homing B cells (CD19+ β7+) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4+ and CD8+ T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-γ responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-γ) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.

scholarly journals Cytokine Profiles for Peripheral Blood Lymphocytes from Patients with Active Pulmonary Tuberculosis and Healthy Household Contacts in Response to the 30-Kilodalton Antigen ofMycobacterium tuberculosis

1998 ◽  
Vol 66 (1) ◽  
pp. 176-180 ◽  
Author(s):  
Martha Torres ◽  
Teresa Herrera ◽  
Hector Villareal ◽  
Elizabeth A. Rich ◽  
Eduardo Sada
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Active Pulmonary Tuberculosis ◽  
Household Contacts ◽  
Reverse Transcription Pcr ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Patients with active tuberculosis (TB) have a stronger humoral but a poorer cellular immune response to the secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis than do healthy household contacts (HHC), who presumably are more protected against disease. The basis for this observation was studied by examining the Th1 (interleukin 2 [IL-2] and gamma interferon [IFN-γ])- and Th2 (IL-10 and IL-4)-type cytokines produced in response to the 30-kDa Ag by peripheral blood mononuclear cells (PBMC) from patients with active pulmonary TB (n = 7) and from HHC who were tuberculin (purified protein derivative) skin test positive (n = 12). Thirty-kilodalton-Ag-stimulated PBMC from TB patients produced significantly lower levels of IFN-γ (none detectable) than did those from HHC (212 ± 73 pg/ml, mean ± standard error) (P < 0.001). Likewise, 30-kDa-Ag-stimulated PBMC from TB patients failed to express IFN-γ mRNA by reverse transcription-PCR, whereas cells from HHC expressed the IFN-γ gene. In contrast, 30-kDa-Ag-stimulated PBMC from TB patients produced significantly higher levels of IL-10 (403 ± 80 pg/ml) than did those from HHC (187 ± 66 pg/ml) (P < 0.013), although cells from both groups expressed the IL-10 gene. IL-2 and IL-4 were not consistently produced, and their genes were not expressed by 30-kDa-Ag-stimulated cells from either TB patients or HHC. After treatment with antituberculous drugs, lymphocytes from four of the seven TB patients proliferated and three of them expressed IFN-γ mRNA in response to the 30-kDa Ag and produced decreased levels of IL-10.

scholarly journals IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells

Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 346-356 ◽  
Author(s):  
Mark A. Brockman ◽  
Douglas S. Kwon ◽  
Daniel P. Tighe ◽  
David F. Pavlik ◽  
Pamela C. Rosato ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Cell Types ◽  
Interleukin 10 ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Multiple Cell

AbstractMurine models indicate that interleukin-10 (IL-10) can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T-cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is up-regulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (NK) cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and -uninfected individuals. These data indicate that multiple cell types contribute to IL-10–mediated immune suppression in the presence of uncontrolled HIV viremia.

scholarly journals Characterization of Humoral and Cellular Immune Responses Elicited by Meningococcal Carriage

2002 ◽  
Vol 70 (3) ◽  
pp. 1301-1309 ◽  
Author(s):  
K. Robinson ◽  
K. R. Neal ◽  
C. Howard ◽  
J. Stockton ◽  
K. Atkinson ◽  
...  
Keyword(s):  
Undergraduate Students ◽  
Mononuclear Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear ◽  
Interleukin 5 ◽  
Whole Cell Lysate ◽  
Intracellular Cytokines ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT In order to study the immune response elicited by asymptomatic carriage of Neisseria meningitidis, samples of serum, peripheral blood mononuclear cells (PBMCs), and saliva were collected from a cohort of more than 200 undergraduate students in Nottingham, United Kingdom, who were subject to high rates of acquisition and carriage of meningococci. Serum immunoglobulin G levels were elevated following increases in the rate of carriage, and these responses were specific for the colonizing strains. In order to investigate T-cell responses, PBMCs from 15 individuals were stimulated with a whole-cell lysate of the H44/76 meningococcal strain (B:15:P1.7,16), stained to detect cell surface markers and intracellular cytokines, and examined by flow cytometry. The cells were analyzed for expression of CD69 (to indicate activation), gamma interferon (IFN-γ) (a representative T-helper 1 subset [Th1]-associated cytokine), and interleukin-5 (IL-5) (a Th2-associated cytokine). Following a brief meningococcal stimulation, the numbers of CD69+ IFN-γ+ CD56/16+ NK cells were much higher than cytokine-positive CD4+ events. Both IFN-γ+ and IL-5+ events were detected among the CD69+ CD4+ population, leading to the conclusion that an unbiased T-helper subset response was elicited by meningococcal carriage.

Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients

2009 ◽  
Vol 390 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Katharina Schroecksnadel ◽  
Christiana Winkler ◽  
Ernst R. Werner ◽  
Mario Sarcletti ◽  
Nikolaus Romani ◽  
...  
Keyword(s):  
Proliferative Response ◽  
Mononuclear Cells ◽  
Interferon Γ ◽  
Pokeweed Mitogen ◽  
Peripheral Blood Mononuclear ◽  
Tryptophan Degradation ◽  
Infected Pbmcs ◽  
Ifn Γ ◽  
And Control

AbstractHIV infection is characterized by progressive immunodeficiency: HIV-infected peripheral blood mononuclear cells (PBMCs) cannot properly react to stimulation with allo-antigens and mitogens. In this study, we examined interferon-γ (IFN-γ)-mediated pathways and the proliferative response of mitogen-stimulated HIV-infected PBMCsin vitro. PBMCs of 30 HIV-infected patients were stimulated with the mitogens concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Mitogen stimulation induced expression of IFN-γ, GTP cyclohydrolase I (GCH-I), and indoleamine (2,3)-dioxygenase (IDO) resulting in enhanced neopterin formation and tryptophan degradation by HIV-infected and control PBMCs. IFN-γ concentrations correlated with neopterin levels and tryptophan degradation. Proliferative responses to PHA and PWM cytokine were lower in HIV patients, with IFN-γ formation predicting proliferative responses. Higher mRNA expression of IFN-γ, GCH-I and IDO after 6 h was related to better proliferative responses in HIV-infected PBMCs. In conclusion, induction of IFN-γ and subsequent enzymes appears to importantly influence the proliferative response of HIV-infected PBMCsin vitro, suggesting a prominent role of the cytokine in the development of immunodeficiency.

scholarly journals Clostridium difficile recurrence is characterized by pro-inflammatory peripheral blood mononuclear cell (PBMC) phenotype

2014 ◽  
Vol 63 (10) ◽  
pp. 1260-1273 ◽  
Author(s):  
Mary B. Yacyshyn ◽  
Tara N. Reddy ◽  
Lauren R. Plageman ◽  
Jiang Wu ◽  
Amy R. Hollar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Clostridium Difficile ◽  
Peripheral Blood ◽  
Cellular Response ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Sample Collection ◽  
Peripheral Blood Mononuclear ◽  
History Of ◽  
Ifn Γ

Clostridium difficile infection (CDI) is a prevalent nosocomial and increasingly community-acquired problem. Little is known about the productive cellular response in patients. We used flow cytometry to define inflammatory (Th1 and Th17) and regulatory [Foxp3+ T-regulatory (Treg)] cells present in circulating peripheral blood mononuclear cells (PBMC) from CDI patients. We consented 67 inpatients that tested either positive or negative for CDI and 16 healthy controls and compared their PBMC phenotypes. PBMC were collected, isolated, and stained for CD3, CD8 and either IL17 (Th17), IFN-γ (Th1) or Foxp3 (Treg) and analysed using flow cytometry. Twenty thousand events were collected in the lymphocyte gate (gate 1) and T-cell phenotypes were defined. CDI patients who clear the primary initial infection have greater numbers of non-CD3 PBMC. CDI patients who develop recurrence of CDI have a greater percentage of CD3+CD8+, CD3+CD4+Foxp3 and fewer low granular CD3−Foxp3+ PBMC. These patients have greater numbers of IFN-γ-producing lymphocytes, as well as PBMC phenotypes represented by increased IFN-γ- and IL17-co-expressing CD4+CD3+. This initial pro-inflammatory phenotype decreases with repeated recurrence, demonstrating importance of timing of sample collection and history of symptoms. Patients with a history of recurrence had increased Foxp3+CD3+CD4+ and IL17+CD3+CD4+ populations. Hence, CDI recurrence is hallmarked by greater numbers of circulating CD3+ lymphocytes skewed towards a Th1/Th17 inflammatory population as well as possible immune plasticity (Th17/Treg).

scholarly journals Characterization of Human Cellular Immune Responses to Novel Mycobacterium tuberculosis Antigens Encoded by Genomic Regions Absent in Mycobacterium bovis BCG

2008 ◽  
Vol 76 (9) ◽  
pp. 4190-4198 ◽  
Author(s):  
R. Al-Attiyah ◽  
A. S. Mustafa
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.

scholarly journals In response to Luteijn et al.: Concerns regarding cGAMP uptake assay and evidence that SLC19A1 is not the major cGAMP importer in human PBMCs

2019 ◽  
Author(s):  
Christopher Ritchie ◽  
Anthony F. Cordova ◽  
Lingyin Li
Keyword(s):  
Mononuclear Cells ◽  
Cell Types ◽  
P Uptake ◽  
Peripheral Blood Mononuclear ◽  
A Genome ◽  
Uptake Assay ◽  
Cyclic Dinucleotides ◽  
Multiple Cell ◽  
Sting Pathway ◽  
Different Cell Types

AbstractWe previously reported that SLC19A1 is an importer of the immunotransmitter 2’3’-cyclic-GMP-AMP (cGAMP)1 by performing a genome wide screen in U937 cells. Soon after, Lutejin et al. reported similar findings by conducting a screen in THP-1 cells2. While the conclusions of these two studies largely overlap, we arrived at significantly different conclusions regarding how broadly SLC19A1 is used by different cell types. Our study suggests that in addition to SLC19A1, many cultured and primary cell types use alternative, unidentified transporters to import cGAMP and other cyclic dinucleotides (CDNs). This conclusion was based on our findings that inhibition of SLC19A1 did not significantly reduce extracellular cGAMP signaling in multiple cell types, including primary CD14+peripheral blood mononuclear cells (PBMCs) from most donors. In contrast, Luteijn et al. concluded that SLC19A1 is the major CDN importer in humans, largely based on their use of a radiolabeled [32P] cGAMP uptake assay. Using this assay, they showed that inhibition of SLC19A1 abolishes [32P] uptake in total PBMCs. However, they did not test whether inhibition of SLC19A1 affects extracellular cGAMP signaling in these cells. Here, we highlight an important issue with the [32P] cGAMP uptake assay used by Luteijn et al. and demonstrate that measuring extracellular cGAMP signaling through the STING pathway is currently the best method for evaluating cGAMP import. We also show that inhibition of SLC19A1 has no effect on extracellular cGAMP signaling in total PBMCs, confirming that this cell type relies on other transport mechanisms for cGAMP import.

scholarly journals Maternal and Foetal Cellular Immune Responses in Dams Infected With High- and Low- Virulence Isolates of Neospora caninum at Mid-Gestation

2021 ◽  
Vol 11 ◽  
Author(s):  
Marta García-Sánchez ◽  
Laura Jiménez-Pelayo ◽  
Patricia Vázquez ◽  
Pilar Horcajo ◽  
Javier Regidor-Cerrillo ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Neospora Caninum ◽  
Response Dynamics ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

Bovine neosporosis is currently considered one of the main causes of abortion in cattle worldwide and the outcome of the infection is, in part, determined by Neospora caninum isolate virulence. However, the dam and foetal immune responses associated with this factor are largely unknown. We used a model of bovine infection at day 110 of gestation to study the early infection dynamics (10- and 20-days post-infection, dpi) after experimental challenge with high- and low-virulence isolates of N. caninum (Nc-Spain7 and Nc-Spain1H, respectively). In the present work, dam peripheral cellular immune responses were monitored twice a week from -1 to 20 dpi. At different time points, IFN-γ and IL-4 production was investigated in stimulated dam blood and the percentage of monocytes, NK cells, B cells and T cells (CD4+, CD8+ and γδ) in peripheral blood mononuclear cells (PBMC) were determined by flow cytometry. In addition, maternal iliofemoral lymph nodes and foetal spleen and thymus were collected at 10 and 20 dpi for the study of the same cell subpopulations. Peripheral immune response dynamics were similar after the infection with both isolates, with a significant increase in the percentage of CD4+ T cells at 6 and 9 dpi in PBMC, coincident with the higher levels of IFN-γ and IL-4 release. However, the levels of IFN-γ were significantly higher and an increase in CD8+ T cells at 9, 13 and 20 dpi was observed in the dams infected with Nc-Spain7. Nc-Spain1H infection induced higher IL4 levels in stimulated blood and a higher CD4+/CD8+ ratio in PBMC. The analysis of the maternal iliofemoral lymph node showed a significant enhancement in the percentage of NK, CD4+ and CD8+ T cells for the animals infected with the highly virulent isolate and euthanized at 20 dpi. Regarding the foetal responses, the most remarkable result was an increase in the percentage of monocytes at 20 dpi in the spleen of foetuses from both infected groups, which suggests that foetuses were able to respond to N. caninum infection at mid gestation. This work provides insights into how isolate virulence affects the maternal and foetal immune responses generated against N. caninum, which may influence the course of infection.

Sign in / Sign up

Export Citation Format

Share Document