Induction of IL-12 Production in Human Peripheral Monocytes byTrypanosoma cruziIs Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γand CD40-CD40L Interactions

Chagas disease, caused by the protozoan parasiteTrypanosoma cruzi(T. cruzi), is characterized by immunopathology driven by IFN-γsecreting Th1-like T cells.T. cruzihas a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described thatT. cruzior its products—like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)—are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γprimed murine macrophages. However, little is known about whetherT. cruzior GPI-mucins exert a similar action in human cells. We therefore decided to further investigate thein vitrocytokine production profile from human mononuclear cells from uninfected donors exposed toT. cruzias well as tGPI-mucins. We observed that both livingT. cruzitrypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ. Our findings suggest that the polarized T1-type cytokine profile seen inT. cruziinfected patients might be a long-term effect of IL-12 production induced by lifelong exposure toT. cruzitGPI-mucins.

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A Limulus Antilipopolysaccharide Factor-Derived Peptide Exhibits a New Immunological Activity with Potential Applicability in Infectious Diseases

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.4.669-675.2000 ◽

2000 ◽

Vol 7 (4) ◽

pp. 669-675 ◽

Cited By ~ 28

Author(s):

Maribel G. Vallespi ◽

Luis A. Glaria ◽

Osvaldo Reyes ◽

Hilda E. Garay ◽

Joel Ferrero ◽

...

Keyword(s):

Infectious Diseases ◽

Cyclic Peptides ◽

Mononuclear Cells ◽

Therapeutic Potential ◽

Peritoneal Macrophages ◽

Induced Response ◽

No Production ◽

Human Mononuclear Cells

ABSTRACT Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF31–52 peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-γ) and IFN-α. Analysis of the effect of LALF31–52 on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF31–52 protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-α levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.

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IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.614165 ◽

2021 ◽

Vol 10 ◽

Author(s):

Manu Kupani ◽

Smriti Sharma ◽

Rajeev Kumar Pandey ◽

Rajiv Kumar ◽

Shyam Sundar ◽

...

Keyword(s):

Nitric Oxide ◽

Visceral Leishmaniasis ◽

Leishmania Donovani ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

No Production ◽

Peripheral Blood Mononuclear ◽

Before And After ◽

Plasma Nitrite

Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production.

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Beyond the Biological Effect of a Chemically Characterized Poplar Propolis: Antibacterial and Antiviral Activity and Comparison with Flurbiprofen in Cytokines Release by LPS-Stimulated Human Mononuclear Cells

Biomedicines ◽

10.3390/biomedicines7040073 ◽

2019 ◽

Vol 7 (4) ◽

pp. 73 ◽

Cited By ~ 2

Author(s):

Paolo Governa ◽

Maria Grazia Cusi ◽

Vittoria Borgonetti ◽

José Mauricio Sforcin ◽

Chiara Terrosi ◽

...

Keyword(s):

Influenza A ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

H1n1 Influenza ◽

Inflammatory Activity ◽

Bacterial Strains ◽

Peripheral Blood Mononuclear ◽

Human Mononuclear Cells ◽

Anti Inflammatory

Bee propolis, especially Euro-Asian poplar propolis, is among the most well-known natural products traditionally used to treat pharyngitis and minor wounds. The aim of this research was to investigate the pharmacological properties responsible for poplar propolis effectiveness using, for the first time, different in vitro approaches applied to a chemically characterized sample. The anti-inflammatory activity was compared with flurbiprofen by determining pro-inflammatory cytokines released by lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMC). The antibacterial activity against Gram+ and Gram- bacteria was assessed, as well as antiviral effects on H1N1 influenza a virus. Poplar propolis (5 and 25 µg/mL) exerted a concentration-dependent anti-inflammatory activity. In this range of concentrations, propolis effect was not inferior to flurbiprofen on cytokines released by lipopolysaccharide (LPS)-stimulated human PBMC. Poplar propolis was found to upregulate IL-6 and IL-1β in non-stimulated PBMC. S. aureus, S. pyogenes, and S. pneumoniae were the most susceptible bacterial strains with inhibitory concentrations ranging from 156 to 625 µg/mL. A direct anti-influenza activity was not clearly seen. Effective anti-inflammatory concentrations of propolis were significantly lower than the antibacterial and antiviral ones and results suggested that the anti-inflammatory activity was the most important feature of poplar propolis linked to its rationale use in medicine.

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In vitro granuloma formation, no production and cytokines profile from human mononuclear cells induced by fractionated antigens of paracoccidioides brasiliensis

Human Immunology ◽

10.1016/s0198-8859(01)00268-3 ◽

2001 ◽

Vol 62 (8) ◽

pp. 799-808 ◽

Cited By ~ 22

Author(s):

Susana N Diniz ◽

Patrı́cia S Cisalpino ◽

Antônio T.F Freire ◽

David N Silva-Teixeira ◽

Christiane Contigli ◽

...

Keyword(s):

Mononuclear Cells ◽

Paracoccidioides Brasiliensis ◽

Granuloma Formation ◽

No Production ◽

Human Mononuclear Cells

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Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K lymphocytes and monocytes are effective against meningococi in cooperation with human imune sera.

Journal of Experimental Medicine ◽

10.1084/jem.150.1.127 ◽

1979 ◽

Vol 150 (1) ◽

pp. 127-137 ◽

Cited By ~ 23

Author(s):

G H Lowell ◽

L F Smith ◽

M S Artenstein ◽

G S Nash ◽

R P MacDermott

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Immune Defense ◽

Peripheral Blood Mononuclear ◽

Effector Cells ◽

Human Mononuclear Cells ◽

Dependent Cell

In cooperation with human heat-inactivated antisera from adults immunized with group C meningococcal polysaccharide, normal human peripheral blood mononuclear cells significantly decreased the viability of group C meningococci (Mgc) in vitro. K lymphocytes (Null cells) and monocytes, (but not T or B lymphocytes) were capable of effecting antibody-dependent cell-mediated (ADC) antibacterial activity in this system. The degree to which meningococcal viability was decreased was a function of the length of the test incubation, the concentration of effector cells, and the amount of antiserum used in the assay. When specific antibodies directed against Mgc were adsorbed from the antiserum, cell-mediated antibacterial activity was abolished. ADC antibacterial activity was also abrogated by performing the assay at 4 degrees C or by heating effector cells to 46 degrees C for 15 min before the assay, Similarities between the ADC antibacterial system and previously described ADCC assays are discussed. The data suggest the K cells (as well as monocytes) may play a role in host immune defense against pathogenic bacteria.

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Chlamydia pneumoniae Infection in Human Monocytes

Infection and Immunity ◽

10.1128/iai.67.3.1445-1449.1999 ◽

1999 ◽

Vol 67 (3) ◽

pp. 1445-1449 ◽

Cited By ~ 82

Author(s):

Sari Airenne ◽

Heljä-Marja Surcel ◽

Hannu Alakärppä ◽

Kirsi Laitinen ◽

Jorma Paavonen ◽

...

Keyword(s):

Chlamydia Pneumoniae ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Immunological Response ◽

Cell Types ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Atherosclerotic Lesions ◽

Transmission Electron

ABSTRACT Chlamydia pneumoniae infection has been associated with cardiovascular diseases in seroepidemiological studies and by demonstration of the pathogen in atherosclerotic lesions. It has the capacity to infect several cell types, including monocyte-derived macrophages, which play an essential role in the development of atherosclerosis. However, the persistence of C. pneumoniaein mononuclear cells is poorly understood. To study the morphology and biological characteristics of the infection, human peripheral blood monocytes were infected with C. pneumoniae. Freshly isolated monocytes resisted the development of infectious progeny, and confocal and transmission electron microscopy showed that the morphology of the inclusions and chlamydial particles was abnormal. Addition of tryptophan or antibodies against gamma interferon did not diminish the inhibition of C. pneumoniae, suggesting that other factors are involved in the chlamydiostatic activity of the monocytes. Chlamydial mRNA was expressed at least 3 days after infection, however, and a capability for infected monocytes to induce a positive lymphocyte proliferative response was detected for up to 7 days, indicating that C. pneumoniae remains metabolically active in the monocytes in vitro. These results are in accordance with the hypothesis that C. pneumoniae may participate in the maintenance of local immunological response and inflammation via infected monocytes and thus enhance atherosclerosis.

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Ultrastructural Changes in Tumor Cells During Human Peripheral Blood Monocyte-Mediated Cytotoxicity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098757 ◽

1981 ◽

Vol 39 ◽

pp. 452-453

Author(s):

K. E. Muse ◽

D. G. Fischer ◽

H. S. Koren

Keyword(s):

Target Cell ◽

Human Peripheral Blood ◽

Mononuclear Phagocytes ◽

Ultrastructural Changes ◽

Target Cells ◽

Limited Information ◽

Blood Monocytes ◽

Tumoricidal Activity ◽

Activated State

Mononuclear phagocytes, a pluripotential cell line, manifest an array of basic extracellular functions. Among these physiological regulatory functions is the expression of spontaneous cytolytic potential against tumor cell targets.The limited observations on human cells, almost exclusively blood monocytes, initially reported limited or a lack of tumoricidal activity in the absence of antibody. More recently, freshly obtained monocytes have been reported to spontaneously impair the biability of tumor target cells in vitro (Harowitz et al., 1979; Montavani et al., 1979; Hammerstrom, 1979). Although the mechanism by which effector cells express cytotoxicity is poorly understood, discrete steps can be distinguished in the process of cell mediated cytotoxicity: recognition and binding of effector to target cells,a lethal-hit stage, and subsequent lysis of the target cell. Other important parameters in monocyte-mediated cytotoxicity include, activated state of the monocyte, effector cell concentrations, and target cell suseptibility. However, limited information is available with regard to the ultrastructural changes accompanying monocyte-mediated cytotoxicity.

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