scholarly journals Gamma Interferon-Regulated Chemokines in Leishmania donovani Infection in the Liver

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Henry W. Murray ◽  
Andrew D. Luster ◽  
Hua Zheng ◽  
Xiaojing Ma
Keyword(s):  
Leishmania Donovani ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Granulomatous Inflammation ◽  
Gamma Interferon ◽  
Content Type ◽  
Cell Recruitment ◽  
Initial Control ◽  
Parasite Replication ◽  
Ifn Γ

ABSTRACT In the livers of C57BL/6 mice, gamma interferon (IFN-γ) controls intracellular Leishmania donovani infection and the efficacy of antimony (Sb) chemotherapy. Since both responses usually correlate with granulomatous inflammation, we tested six prominently expressed, IFN-γ-regulated chemokines—CXCL9, CXCL10, CXCL13, CXCL16, CCL2, and CCL5—for their roles in (i) mononuclear cell recruitment and granuloma assembly and maturation, (ii) initial control of infection and self-cure, and (iii) responsiveness to Sb treatment. Together, the results for the L. donovani-infected livers of chemokine-deficient mice (CXCR6−/− mice were used as CXCL16-deficient surrogates) indicated that individual IFN-γ-induced chemokines have diverse affects and (i) may be entirely dispensable (CXCL13, CXCL16), (ii) may promote (CXCL10, CCL2, CCL5) or downregulate (CXCL9) initial granuloma assembly, (iii) may enhance (CCL2, CCL5) or hinder (CXCL10) early parasite control, (iv) may promote granuloma maturation (CCL2, CCL5), (v) may exert a granuloma-independent action that enables self-cure (CCL5), and (vi) may have no role in responsiveness to chemotherapy. Despite the near absence of tissue inflammation in early-stage infection, parasite replication could be controlled (in CXCL10−/− mice) and Sb was fully active (in CXCL10−/−, CCL2−/−, and CCL5−/− mice). These results characterize chemokine action in the response to L. donovani and also reemphasize that (i) recruited mononuclear cells and granulomas are not required to control infection or respond to Sb chemotherapy, (ii) granuloma assembly, control of infection, and Sb's efficacy are not invariably linked expressions of the same T cell-dependent, cytokine-mediated antileishmanial mechanism, and (iii) granulomas are not necessarily hallmarks of protective antileishmanial immunity.

scholarly journals Granzyme-Mediated Regulation of Host Defense in the Liver in Experimental Leishmania donovani Infection

2014 ◽  
Vol 83 (2) ◽  
pp. 702-712 ◽  
Author(s):  
Henry W. Murray ◽  
Marisa Mitchell-Flack ◽  
Hua Zheng ◽  
Xiaojing Ma
Keyword(s):  
Host Defense ◽  
Leishmania Donovani ◽  
Early Stage ◽  
Acquired Resistance ◽  
Double Knockout ◽  
Th1 Cell ◽  
Content Type ◽  
Infected Liver ◽  
Parasite Replication ◽  
Cell Effector Function

In the livers of susceptible C57BL/6 (B6) mice infected withLeishmania donovani, CD8+T cell mechanisms are required for granuloma assembly, macrophage activation, intracellular parasite killing, and self-cure. Since gene expression of perforin and granzymes A and B (GzmA and GzmB), cytolytic proteins linked to CD8+cell effector function, was enhanced in infected liver tissue, B6 mice deficient in these granular proteins were used to gauge host defense roles. Neither perforin nor GzmA was required; however, mice deficient in GzmB (GzmB−/−, GzmB cluster−/−, and GzmA×B cluster double knockout [DKO] mice) showed both delayed granuloma assembly and initially impaired control of parasite replication. Since these two defects in B6 mice were limited to early-stage infection, innately resistant 129/Sv mice were also tested. In this genetic setting, expression of both innate and subsequent T (Th1) cell-dependent acquired resistance, including the self-cure phenotype, was entirely derailed in GzmA×B cluster DKO mice. These results, in susceptible B6 mice for GzmB and in resistant 129/Sv mice for GzmA and/or the GzmB cluster, point to granzyme-mediated host defense regulation in the liver in experimental visceral leishmaniasis.

scholarly journals Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

2012 ◽  
Vol 19 (11) ◽  
pp. 1889-1893 ◽  
Author(s):  
Kaarina Ranta ◽  
Kaisa Nieminen ◽  
Filip S. Ekholm ◽  
Moniká Poláková ◽  
Mattias U. Roslund ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Mouse Macrophages ◽  
Ifn Γ ◽  
Low Levels ◽  
Necrosis Factor

ABSTRACTImmunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

scholarly journals MicroRNA 155 Contributes to Host Immunity against Leishmania donovani but Is Not Essential for Resolution of Infection

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Sanjay Varikuti ◽  
Gayathri Natarajan ◽  
Greta Volpedo ◽  
Bhawana Singh ◽  
Omar Hamza ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Interleukin 4 ◽  
Cytokine Signaling ◽  
T Helper 1 ◽  
Content Type ◽  
Inflammatory Monocytes ◽  
Organ Specific ◽  
Src Homology ◽  
Ifn Γ ◽  
Src Homology 2 Domain

ABSTRACT CD4+ T helper 1 (Th1) cells producing interferon gamma (IFN-γ) are critical for the resolution of visceral leishmaniasis (VL). MicroRNA 155 (miR155) promotes CD4+ Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL. To determine the role of miR155 in VL, we monitored the course of Leishmania donovani infection in miR155 knockout (miR155KO) and wild-type (WT) C57BL/6 mice. miR155KO mice displayed significantly higher liver and spleen parasite loads than WT controls and showed impaired hepatic granuloma formation. However, parasite growth eventually declined in miR155KO mice, suggesting the induction of a compensatory miR155-independent antileishmanial pathway. Leishmania antigen-stimulated splenocytes from miR155KO mice produced significantly lower levels of Th1-associated IFN-γ than controls. Interestingly, at later time points, levels of Th2-associated interleukin-4 (IL-4) and IL-10 were also lower in miR155KO splenocyte supernatants than in WT mice. On the other hand, miR155KO mice displayed significantly higher levels of IFN-γ, iNOS, and TNF-α gene transcripts in their livers than WT mice, indicating that distinct organ-specific antiparasitic mechanisms were involved in control of L. donovani infection in miR155KO mice. Throughout the course of infection, organs of miR155KO mice showed significantly more PDL1-expressing Ly6Chi inflammatory monocytes than WT mice. Conversely, blockade of Ly6Chi inflammatory monocyte recruitment in miR155KO mice significantly reduced parasitic loads, indicating that these cells contributed to disease susceptibility. In conclusion, we found that miR155 contributes to the control of L. donovani but is not essential for infection resolution.

scholarly journals Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jennifer D. Helble ◽  
Rodrigo J. Gonzalez ◽  
Ulrich H. von Andrian ◽  
Michael N. Starnbach
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Chlamydia Trachomatis ◽  
Genital Tract ◽  
Gamma Interferon ◽  
Cell Homing ◽  
Content Type ◽  
T Cell Homing ◽  
Ifn Γ

ABSTRACT While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.

scholarly journals Lactobacilli and Streptococci Induce Interleukin-12 (IL-12), IL-18, and Gamma Interferon Production in Human Peripheral Blood Mononuclear Cells

1998 ◽  
Vol 66 (12) ◽  
pp. 6058-6062 ◽  
Author(s):  
Minja Miettinen ◽  
Sampsa Matikainen ◽  
Jaana Vuopio-Varkila ◽  
Jaana Pirhonen ◽  
Kari Varkila ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Protein Production ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Gamma Interferon ◽  
Cytokine Gene Expression ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACT Human peripheral blood mononuclear cells (PBMC) were stimulated with three nonpathogenic Lactobacillus strains and with one pathogenic Streptococcus pyogenes strain, and cytokine gene expression and protein production were analyzed. All bacteria strongly induced interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha mRNA expression and protein production. S. pyogenes was the most potent inducer of secretion of IL-12 and gamma interferon (IFN-γ), and two of three Lactobacillusstrains induced IL-12 and IFN-γ production. All strains induced IL-18 protein production. IL-10 and IL-4 production was induced weakly and not at all, respectively. Our data show that nonpathogenic lactobacilli and pathogenic streptococci can induce Th1 type cytokines IL-12, IL-18, and IFN-γ in human PBMC.

scholarly journals GABARAPL2 Is Critical for Growth Restriction of Toxoplasma gondii in HeLa Cells Treated with Gamma Interferon

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Zhaoxia Zhang ◽  
Haorong Gu ◽  
Qi Li ◽  
Jun Zheng ◽  
Shinuo Cao ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Hela Cells ◽  
Critical Role ◽  
Gamma Interferon ◽  
Growth Restriction ◽  
Membrane Structures ◽  
Content Type ◽  
Receptor Associated Protein ◽  
Ifn Γ ◽  
And Function

ABSTRACT Gamma interferon (IFN-γ)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN-γ stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that γ-aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN-γ-treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IFN-γ -induced immune response. These findings provide further understanding of a noncanonical autophagy pathway responsible for IFN-γ-dependent inhibition of T. gondii growth in human HeLa cells and demonstrate the critical role of GABARAPL2 in this response.

scholarly journals Th1/Th2 Cytokine Profile in Patients Coinfected with HIV and Leishmania in Brazil

2011 ◽  
Vol 18 (10) ◽  
pp. 1765-1769 ◽  
Author(s):  
Maria Zilma Andrade Rodrigues ◽  
Maria Fernanda Rios Grassi ◽  
Sanjay Mehta ◽  
Xing-Quan Zhang ◽  
Luana Leandro Gois ◽  
...  
Keyword(s):  
Immune Responses ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Th2 Cytokine ◽  
Cytokine Levels ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACTTo evaluate the effects of HIV on immune responses in cutaneous leishmaniasis (CL), we quantified cytokine levels from plasma and stimulated peripheral blood mononuclear cells (PBMCs) from individuals infected with HIV and/or CL. Gamma interferon (IFN-γ) and interleukin 13 (IL-13) levels and the ratio of IFN-γ to IL-10 produced in response to stimulation with solubleLeishmaniaantigens were significantly lower in HIV-Leishmania-coinfected patients than in CL-monoinfected patients.

scholarly journals Immune Responses of Iranian Patients with Visceral Leishmaniasis and Recovered Individuals to LCR1 of Leishmania infantum

2014 ◽  
Vol 21 (4) ◽  
pp. 518-525 ◽  
Author(s):  
Hamid M. Niknam ◽  
Firoozeh Abrishami ◽  
Mohammad Doroudian ◽  
Mosayeb Rostamian ◽  
Maryam Moradi ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Immune Responses ◽  
Leishmania Infantum ◽  
Mononuclear Cells ◽  
Antibody Responses ◽  
Antibody Detection ◽  
Recent History ◽  
Content Type ◽  
History Of ◽  
Ifn Γ

ABSTRACTVisceral leishmaniasis is a serious public health problem.Leishmania infantumis one of its causative agents. LCR1 is an immunogen fromL. infantum. Antibodies against this protein have been detected in visceral leishmaniasis patients. The aim of this study was to define the antibody and cellular immune responses against LCR1 in Iranian visceral leishmaniasis patients and recovered individuals. The LCR1 protein was produced in recombinant form. Antibody responses against this protein were studied in Iranian individuals with a recent history of visceral leishmaniasis. Responses of peripheral blood mononuclear cells to this protein were studied in Iranian individuals who had recovered from visceral leishmaniasis. Our data show that (i) there was an antibody response to LCR1 in each individual with a recent history of visceral leishmaniasis studied, (ii) there was neither a proliferative response nor production of gamma interferon (IFN-γ) or interleukin 10 in response to LCR1 by mononuclear cells from individuals who had recovered from visceral leishmaniasis, and (iii) individuals who have recovered from visceral leishmaniasis show ongoing immune responses long after recovery from the disease. These data show that there are no detectable cellular memory responses to LCR1 in Iranian individuals who have recovered from visceral leishmaniasis, while there are detectable antibody responses in patients with this disease. Our data suggest that LCR1 has potential applications for the diagnosis of leishmaniasis through antibody detection, while the application of LCR1 alone for induction of IFN-γ in individuals who recovered from this disease is not supported. The presence of long-lasting immune reactivities in individuals who recovered from the disease may show the necessity of extended medical surveillance for these individuals.

scholarly journals Disruption of Interleukin-27 Signaling Results in Impaired Gamma Interferon Production but Does Not Significantly Affect Immunopathology in Murine Schistosome Infection

2007 ◽  
Vol 75 (6) ◽  
pp. 3169-3177 ◽  
Author(s):  
Mara G. Shainheit ◽  
Rosita Saraceno ◽  
Lindsey E. Bazzone ◽  
Laura I. Rutitzky ◽  
Miguel J. Stadecker
Keyword(s):  
T Cells ◽  
Proinflammatory Cytokines ◽  
Cd4 T Cells ◽  
Granulomatous Inflammation ◽  
Gamma Interferon ◽  
Mouse Strains ◽  
Interleukin 17 ◽  
Schistosome Infection ◽  
Ifn Γ

ABSTRACT In schistosomiasis mansoni, parasite eggs cause hepatointestinal granulomatous inflammation and fibrosis mediated by CD4 T cells specific for egg antigens. The severity of disease varies extensively in humans and among mouse strains. Marked disease exacerbation induced in typically low-pathology C57BL/6 mice by immunization with schistosome egg antigens (SEA) in complete Freund's adjuvant (SEA/CFA) correlates with elevated production of the proinflammatory cytokines gamma interferon (IFN-γ) and interleukin-17 (IL-17), which are regulated by IL-12 and IL-23, respectively. Here we examined the effect on the schistosome infection of a third member of the IL-12 family of heterodimeric cytokines, IL-27, using SEA/CFA-immunized and unimmunized mice deficient in the IL-27 receptor chain WSX-1 (WSX-1−/−). SEA-stimulated bulk mesenteric lymph node cells or CD4 T cells from 7-week-infected WSX-1−/− mice produced significantly less IFN-γ than did those from C57BL/6 mice, even though there was no difference between these mice in exacerbated hepatic egg-induced granulomatous inflammation or in the levels of IL-17 induced by immunization with SEA/CFA. A fraction of the cells in the granulomas stained positive for IL-27, but there were no significant differences between WSX-1−/− and BL/6 mice, nor were there differences in the number of CD4 T cells and eosinophils. A 24-week chronic infection resulted in markedly reduced levels of proinflammatory cytokines, including IFN-γ, in WSX-1−/− mice, but again the magnitude of immunopathology was not significantly different between the two groups. These findings indicate that despite the impaired IFN-γ production, IL-27 signaling has no significant effect on either the magnitude of egg-induced immunopathology or on its closest in vitro correlate, IL-17.

scholarly journals Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype

2013 ◽  
Vol 81 (10) ◽  
pp. 3750-3756 ◽  
Author(s):  
Arjan van Laarhoven ◽  
Jornt J. Mandemakers ◽  
Johanneke Kleinnijenhuis ◽  
Mimount Enaimi ◽  
Ekta Lachmandas ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Selective Advantage ◽  
Beijing Genotype ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Tnf Α ◽  
Evolutionary Success ◽  
Ifn Γ

ABSTRACTOne of the most widespread clades ofMycobacterium tuberculosisworldwide, the Beijing genotype family, consists of ancient (atypical) and modern (typical) strains. Modern Beijing strains outcompete ancient strains in terms of prevalence, while reserving a higher degree of genetic conservation. We hypothesize that their selective advantage lies in eliciting a different host immune response. Bead-disrupted lysates of a collection of differentM. tuberculosisstrains of the modern (n= 7) or ancient (n= 7) Beijing genotype, as well as the Euro-American lineage (n= 6), were used for induction ofex vivocytokine production in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals. Hierarchical clustering and multivariate regression analyses were used to study possible differences in production of nine cytokines. Modern and ancientM. tuberculosisBeijing genotypes induced different cytokine signatures. Overall induction of interleukin-1β (IL-1β), gamma interferon (IFN-γ), and IL-22 was 38 to 40% lower after stimulation with modern Beijing strains (correctedPvalues of <0.0001, 0.0288, and 0.0002, respectively). Euro-American reactivation strains induced 2-fold more TNF-α production than both types of Beijing strains. The observed differences in cytokine induction point to a reduction in proinflammatory cytokine response as a possible contributing factor to the evolutionary success of modern Beijing strains.

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