scholarly journals Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function

2010 ◽  
Vol 78 (7) ◽  
pp. 3272-3279 ◽  
Author(s):  
Manuel Rodríguez-Zapata ◽  
Marlene J. Matías ◽  
Alfredo Prieto ◽  
Marco A. Jonde ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Phagocytic Activity ◽  
Human Brucellosis ◽  
Blood Monocytes ◽  
Phagocytic Cells ◽  
Necrosis Factor Alpha ◽  
Th1 Response ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1β (IL-1β), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-γ, IL-2, and TNF-α, but not that of IL-4, by phorbol myristate-activated CD4+ CD3+ and CD8+ CD3+ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-γ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.

scholarly journals Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis

2001 ◽  
Vol 69 (5) ◽  
pp. 3232-3239 ◽  
Author(s):  
R. L. A. Bottrel ◽  
W. O. Dutra ◽  
F. A. Martins ◽  
B. Gontijo ◽  
E. Carvalho ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cutaneous Leishmaniasis ◽  
Ex Vivo ◽  
Protozoan Parasite ◽  
Recombinant Antigen ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Leishmaniasis, caused by infection with the protozoan parasiteLeishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-γ) production by several different sources, listed in order of contribution: CD4+ T lymphocytes, CD4−, CD8− lymphocytes, and CD8+ T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-γ and tumor necrosis factor alpha (TNF-α) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4+ T lymphocytes (IFN-γ+ and IL-10−/IL-4−), Tc1 CD8+ T cells (IFN-γ+, and IL-10−/IL-4−), and a high frequency of TNF-α-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.

scholarly journals Microfilariae of the Filarial Nematode Litomosoides sigmodontis Exacerbate the Course of Lipopolysaccharide-Induced Sepsis in Mice

2008 ◽  
Vol 76 (4) ◽  
pp. 1668-1677 ◽  
Author(s):  
Marc P. Hübner ◽  
Bastian Pasche ◽  
Svetoslav Kalaydjiev ◽  
Peter T. Soboslay ◽  
Andreas Lengeling ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Female Adult ◽  
Necrosis Factor Alpha ◽  
Lps Challenge ◽  
Litomosoides Sigmodontis ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than sham-treated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilaria-releasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN-γ receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN-γ and TNF-α. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood.

scholarly journals Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Lance Nesbit ◽  
Suzanne M. Johnson ◽  
Demosthenes Pappagianis ◽  
Neil M. Ampel
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
High Expression ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDCT27K) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDCT27K did significantly increase the concentrations of IL-2 and IFN-γ released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.

scholarly journals Inflammatory Cytokines Enhance the Interaction of Mannheimia haemolytica Leukotoxin with Bovine Peripheral Blood Neutrophils In Vitro

2002 ◽  
Vol 70 (8) ◽  
pp. 4336-4343 ◽  
Author(s):  
F. Leite ◽  
S. O'Brien ◽  
M. J. Sylte ◽  
T. Page ◽  
D. Atapattu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Biological Response ◽  
Lymphocyte Function ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Blood Neutrophils ◽  
Ifn Γ ◽  
Bovine Pneumonic Pasteurellosis

ABSTRACT Mannheimia (Pasteurella) haemolytica A1 produces several virulence factors that play an important role in the pathogenesis of bovine pneumonic pasteurellosis. Foremost among these is a leukotoxin (LKT) that specifically kills ruminant leukocytes. Recent evidence suggests that M. haemolytica LKT binding to bovine leukocytes is mediated by the β2-integrin CD11a/CD18 (lymphocyte function-associated antigen 1 [LFA-1]), which subsequently induces activation and cytolysis of these cells. Inflammatory cytokines, which are released during viral and bacterial infection, are reported to increase LFA-1 expression and conformational activation. We investigated the effects of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) on the interaction of M. haemolytica LKT with bovine peripheral blood neutrophils (PMNs). In this study we demonstrated, by flow cytometry, that bovine PMNs increased their binding to an anti-bovine LFA-1 monoclonal antibody (BAT75A) following in vitro incubation with IL-1β, TNF-α, or IFN-γ. Incubation with cytokines also increased CD18 expression, as assessed by real-time PCR and by Western blotting. Increased LFA-1 expression by PMNs exposed to cytokines was associated with increased LKT binding and cytotoxicity. The latter represented, at least in part, enhanced PMN apoptosis, as assessed by propidium iodine staining and caspase-3 activation. The results of this study suggest that inflammatory cytokines may play an important role in enhancing the biological response of bovine PMNs to M. haemolytica LKT.

scholarly journals Modulation of Cytokine Response of Pneumonic Foals by Virulent Rhodococcus equi

1999 ◽  
Vol 67 (10) ◽  
pp. 5041-5047 ◽  
Author(s):  
Steeve Giguère ◽  
Bruce N. Wilkie ◽  
John F. Prescott
Keyword(s):  
T Lymphocytes ◽  
Mrna Expression ◽  
Rhodococcus Equi ◽  
Cytokine Response ◽  
Interleukin 12 ◽  
Virulence Plasmid ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ

ABSTRACT The ability of Rhodococcus equi to induce pneumonia in foals depends on the presence of an 85- to 90-kb plasmid. In this study, we evaluated whether plasmid-encoded products mediate virulence by modulating the cytokine response of foals. Foals infected intrabronchially with a virulence plasmid-containing strain of R. equi had similar gamma interferon (IFN-γ) and interleukin-12 (IL-12) p35 but significantly higher IL-1β, IL-10, IL-12 p40, and tumor necrosis factor alpha (TNF-α) mRNA expression in lung tissue compared to foals infected with the plasmid-cured derivative. IFN-γ mRNA expression levels in CD4+ T lymphocytes isolated from bronchial lymph nodes (BLN) were similar for the two groups of R. equi-infected foals on day 3 postinfection. However, on day 14, in association with pneumonia and marked multiplication of virulentR. equi but with complete clearance of the plasmid-cured derivative, IFN-γ mRNA expression in BLN CD4+ T lymphocytes was significantly (P < 0.001) higher in foals infected with the plasmid-cured derivative. These results suggests an immunomodulating role for R. equi virulence plasmid-encoded products in downregulating IFN-γ mRNA expression by CD4+ T lymphocytes.

scholarly journals Expression of Toll-Like Receptor 4, Tumor Necrosis Factor-Alpha, Matrix Metalloproteinase-9 and Effects of Benazepril in Patients with Acute Coronary Syndromes

2010 ◽  
Vol 4 ◽  
pp. CMC.S5659 ◽  
Author(s):  
Ping Xie ◽  
Yun-Shan Cao ◽  
Peng Su ◽  
Yu-Hong Li ◽  
Zhi-Ling Gao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Peripheral Blood ◽  
Serum Levels ◽  
Control Group ◽  
Blood Monocytes ◽  
Necrosis Factor Alpha ◽  
Peripheral Blood Monocytes ◽  
Regular Treatment ◽  
Tnf Α ◽  
Coronary Syndromes

Objectives The study aims to explore the relationship between expressions of toll-like receptor 4 (TLR4) on peripheral blood monocytes, serum tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) in patients with acute coronary syndromes(ACS), and to investigate the possible mechanisms of Benazepril stabilizing atherosclerosis plaques. Methods 70 patients selected were randomly divided into Benazepril treatment group (35 patients) and regular treatment group (35 patients). Meanwhile, Stable angina pectoris (SAP) group of 32 patients and control group of 22 patients were also set up. With the help of flow-cytometry, expressions of TLR4 on peripheral blood monocytes of the four groups were analyzed and compared to show differences, correlations and changes of the above mentioned indicators. The concentration of TNF-α and MMP-9 in serum were measured by enzyme linked immunosorbent assay (ELISA). Results (1) Expressions of TLR4, levels of TNF-α and MMP-9 were increased and the rate was rising from the control group, to SAP group and then to ACS group. All these indicators in ACS group are significantly higher than those in other groups ( P < 0.05). (ACS versus SAP, control; all ( P < 0.05). (2) Multi-linear regression analysis indicates that there was a positive correlation between the expression level of TLR4 and serum levels of TNF-α and MMP-9 in patients with ACS ( P < 0.01). (3) There is no significant differences between the expression level of TLR4 and serum levels of TNF-α and MMP-9 in Benazepril treatment group and regular treatment group before treatment ( P > 0.05) while they all fell after treatment ( P < 0.05). In addition, all the indicators decreased more greatly than the regular treatment group. Conclusions TLR4 on peripheral blood monocytes and serum TNF-α and MMP-9 in patients with coronary arteriosclerosis disease may be effective markers of the vulnerable plaque. Benazepril can inhibit over-expression of TLR4 and reduce serum levels of TNF-α and MMP-9, thus stabilize the vulnerable plaques and improve the condition of the patients with ACS.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

scholarly journals Evaluation of the phagocytic activity of peripheral blood monocytes of patients with Jorge Lobo's disease

2004 ◽  
Vol 37 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Fátima Regina Vilani-Moreno ◽  
Luciana Moreira Silva ◽  
Diltor Vladimir Araújo Opromolla
Keyword(s):  
Incubation Time ◽  
Peripheral Blood ◽  
Phagocytic Activity ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Significant Difference ◽  
Host Parasite ◽  
And Control

Studies on host-parasite interaction in Jorge Lobo's disease are scarce, with no report in the literature on the phagocytosis of Lacazia loboi by phagocytic mononuclear cells. Thus, the objective of the present study was to assess the phagocytic activity of blood monocytes in the presence of L. loboi in patients with the disease and in healthy subjects (controls) over 3 and 24 hours of incubation. Statistical analyses of the results showed no significant difference in percent phagocytosis of the fungus between patient and control monocytes. With respect to incubation time, however, there was a significant difference, in that percent phagocytosis was higher at 3 hours than at 24 hours (p <0.01). These results suggest that monocytes from patients with the mycosis are able to phagocyte the fungus, as also observed in control individuals.

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