scholarly journals Role of Gamma Interferon and Interleukin-4 in Host Defense against the Human Filarial Parasite Brugia malayi

2000 ◽  
Vol 68 (5) ◽  
pp. 3034-3035 ◽  
Author(s):  
Subash Babu ◽  
Lisa M. Ganley ◽  
Thomas R. Klei ◽  
Leonard D. Shultz ◽  
T. V. Rajan
Keyword(s):  
Host Defense ◽  
Brugia Malayi ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Ifn Γ ◽  
Canonical Type ◽  
Time Required

ABSTRACT We have investigated the roles of gamma interferon (IFN-γ) and interleukin-4 (IL-4) in host defense against Brugia malayi. Our data suggest that the lack of either IFN-γ or IL-4 prolongs the time required to achieve sterile immunity, suggesting that both canonical type 1 and type 2 responses are involved in the clearance of infection.

scholarly journals Differential Cytokine Pattern in the Spleens and Livers of BALB/c Mice Infected with Penicillium marneffei: Protective Role of Gamma Interferon

2003 ◽  
Vol 71 (1) ◽  
pp. 465-473 ◽  
Author(s):  
Francesca Sisto ◽  
Annarita Miluzio ◽  
Orazio Leopardi ◽  
Maurizio Mirra ◽  
Johan R. Boelaert ◽  
...  
Keyword(s):  
Immune Response ◽  
Gamma Interferon ◽  
Penicillium Marneffei ◽  
Yeast Cells ◽  
Interleukin 12 ◽  
Type 2 Cytokines ◽  
Ifn Γ

ABSTRACT Penicillium marneffei is an intracellular opportunistic fungus causing invasive mycosis in AIDS patients. T cells and macrophages are important for protection in vivo. However, the role of T-cell cytokines in the immune response against P. marneffei is still unknown. We studied by semiquantitative reverse transcription-PCR and biological assays the patterns of expression of Th1 and Th2 cytokines in the organs of wild-type (wt) and gamma interferon (IFN-γ) knockout (GKO) mice infected intravenously with P. marneffei conidia. At 3 × 105 conidia/mouse, a self-limiting infection developed in wt BALB/c mice, whereas all GKO mice died at day 18 postinoculation. Splenic and hepatic granulomas were present in wt mice, whereas disorganized masses of macrophages and yeast cells were detected in GKO mice. The infection resolved faster in the spleens than in the livers of wt mice and was associated with the local expression of type 1 cytokines (high levels of interleukin-12 [IL-12] and IFN-γ) but not type 2 cytokines (low levels of IL-4 and IL-10). Conversely, both type 1 and type 2 cytokines were detected in the livers of wt animals. Disregulation of the cytokine profile was seen in the spleens but not in the livers of GKO mice. The inducible nitric oxide synthase mRNA level was low and the TNF-α level was high in both spleens and livers of GKO mice compared to wt mice. These data suggest that the polarization of a protective type 1 immune response against P. marneffei is regulated at the level of individual organs and that the absence of IFN-γ is crucial for the activation of fungicidal macrophages and the development of granulomas.

scholarly journals Populations of Human T Lymphocytes That Traverse the Vascular Endothelium Stimulated by Borrelia burgdorferi Are Enriched with Cells That Secrete Gamma Interferon

2004 ◽  
Vol 72 (3) ◽  
pp. 1530-1536 ◽  
Author(s):  
Edna I. Gergel ◽  
Martha B. Furie
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Vascular Endothelium ◽  
Human Peripheral Blood ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Ifn Γ

ABSTRACT Some diseases are characterized by prevalence in the affected tissues of type 1 T lymphocytes, which secrete gamma interferon (IFN-γ) and other proinflammatory cytokines. For example, type 1 T cells predominate in the lesions of patients with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used an in vitro model of the blood vessel wall to test the premise that the vascular endothelium actively recruits circulating type 1 T cells to such lesions. When T lymphocytes isolated from human peripheral blood were examined, the populations that traversed monolayers of resting human umbilical vein endothelial cells (HUVEC) or HUVEC stimulated by interleukin-1β or B. burgdorferi were markedly enriched for T cells that produced IFN-γ compared to the initially added population of T cells. No enrichment was seen for cells that produced interleukin-4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins mediated passage of the T cells across both resting and stimulated HUVEC, and the endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was responsible for the enhanced migration of T cells across stimulated HUVEC. These results suggest that the vascular endothelium may contribute to the selective accumulation of type 1 T cells in certain pathological lesions, including those of Lyme disease.

scholarly journals Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis

2000 ◽  
Vol 68 (9) ◽  
pp. 5393-5400 ◽  
Author(s):  
S. G. Rhodes ◽  
N. Palmer ◽  
S. P. Graham ◽  
A. E. Bianco ◽  
R. G. Hewinson ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Early Increase ◽  
Onchocerca Ochengi ◽  
Ifn Γ ◽  
Bovine Tuberculin ◽  
Kinetics Of ◽  
Experimental Challenge

ABSTRACT This study shows that gamma interferon (IFN-γ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-γ and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-γ was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-γ responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-γ and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of theM. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans

2005 ◽  
Vol 98 (2) ◽  
pp. 565-571 ◽  
Author(s):  
G. I. Lancaster ◽  
Q. Khan ◽  
P. T. Drysdale ◽  
F. Wallace ◽  
A. E. Jeukendrup ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytokine Production ◽  
Stress Hormone ◽  
Induced Stress ◽  
Ifn Γ ◽  
Exercise Induced

The present study was undertaken to examine the role of the exercise-induced stress hormone response on the regulation of type 1 and type 2 T lymphocyte intracellular cytokine production. Subjects performed 2.5 h of cycling exercise at 65% maximal O2 uptake while ingesting a 6.4% carbohydrate (CHO) solution, 12.8% CHO solution, or a placebo. Peripheral whole blood samples were stimulated and stained for T lymphocyte surface antigens (CD4 and CD8). Cells were then permeabilized, stained for intracellular cytokines, and analyzed using flow cytometry. Exercise resulted in a decrease ( P < 0.05) in the number and percentage of IFN-γ positive CD4+ and CD8+ T lymphocytes. These stimulated cells produced less IFN-γ immediately postexercise ( P < 0.05) and 2-h postexercise ( P < 0.05) compared with preexercise. However, CHO ingestion, which attenuated the exercise-induced stress hormone response compared with placebo ( P < 0.05), prevented both the decrease in the number and percentage of IFN-γ-positive CD4+ and CD8+ T lymphocytes and the suppression of IFN-γ production from stimulated CD4+ and CD8+ T lymphocytes. There was no effect of exercise on the number of, or cytokine production from, IL-4-positive CD4+ or CD8+ T lymphocytes. These data provide support for the role of exercise-induced elevations in stress hormones in the regulation of type 1 T lymphocyte cytokine production and distribution.

scholarly journals LACK-Specific CD4+ T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection

2002 ◽  
Vol 70 (6) ◽  
pp. 3122-3129 ◽  
Author(s):  
Eliane Bourreau ◽  
Ghislaine Prévot ◽  
Jacques Gardon ◽  
Roger Pradinaud ◽  
Hitoshi Hasagewa ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Effector Memory ◽  
Cellular Source ◽  
Effector Memory Cells ◽  
Ifn Γ

ABSTRACT The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis. Gamma interferon (IFN-γ) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4+ cells producing IFN-γ were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4+ T cells producing IFN-γ and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA− CCR7− CD4+ T cells. CD4+ T cells producing IFN-γ are CD62L−, and CD4+ T cells producing IL-10 are CD62L+, indicating that these cells have different tissue-homing capacities. These findings show that SLA and LACK induce both type 1 (IFN-γ) and type 2 (IL-10 or IL-13) cell responses.

Type 2 immune response associated with silicosis is not instrumental in the development of the disease

2007 ◽  
Vol 292 (1) ◽  
pp. L107-L113 ◽  
Author(s):  
Pierre Misson ◽  
Frank Brombacher ◽  
Monique Delos ◽  
Dominique Lison ◽  
Francois Huaux
Keyword(s):  
Immune Response ◽  
Lung Fibrosis ◽  
Receptor Expression ◽  
Fibrotic Disease ◽  
Pulmonary Response ◽  
Type 2 Immune Response ◽  
Ifn Γ

It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4−/− mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor α (IL-4Rα), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG1) in the lungs of IL-4−/− and IL-4Rα−/− mice did not affect the development of the disease. Measurement of IL-13α2 receptor expression and IgG2a, IL-12p70, and IFN-γ levels in silica-treated IL-4−/− and IL-4Rα−/− animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.

scholarly journals Impaired Host Defense, Hematopoiesis, Granulomatous Inflammation and Type 1–Type 2 Cytokine Balance in Mice Lacking CC Chemokine Receptor 1

1997 ◽  
Vol 185 (11) ◽  
pp. 1959-1968 ◽  
Author(s):  
Ji-Liang Gao ◽  
Thomas A. Wynn ◽  
Yun Chang ◽  
Eric J. Lee ◽  
Hal E. Broxmeyer ◽  
...  
Keyword(s):  
Host Defense ◽  
Chemokine Receptor ◽  
Specific Antigen ◽  
Granulomatous Inflammation ◽  
Interleukin 4 ◽  
Cc Chemokine ◽  
Cytokine Balance ◽  
Chemokine Receptor 1

CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and hematopoiesis regulator macrophage inflammatory protein (MIP)-1α, as well as several related CC chemokines. Four other CCR subtypes are known; their leukocyte and chemokine specificities overlap with, but are not identical to, CCR1, suggesting that CCR1 has both redundant and specific biologic roles. To test this, we have developed CCR1-deficient mice (−/−) by targeted gene disruption. Although the distribution of mature leukocytes was normal, steady state and induced trafficking and proliferation of myeloid progenitor cells were disordered in −/− mice. Moreover, mature neutrophils from −/− mice failed to chemotax in vitro and failed to mobilize into peripheral blood in vivo in response to MIP-1α. Consistent with this, −/− mice had accelerated mortality when challenged with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni eggs intravenously, and observed a 40% reduction in the size of lung granulomas in −/− mice compared to +/+ littermates. This was associated with increased interferon-γ and decreased interleukin-4 production in −/− versus +/+ lung lymph node cells stimulated with egg-specific antigen, suggesting that CCR1 influences the inflammatory response not only through direct effects on leukocyte chemotaxis, but also through effects on the type 1–type 2 cytokine balance. Thus CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation.

scholarly journals Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia

2000 ◽  
Vol 68 (4) ◽  
pp. 1827-1833 ◽  
Author(s):  
Mustafa Akkoyunlu ◽  
Erol Fikrig
Keyword(s):  
Gamma Interferon ◽  
Cytokine Response ◽  
Interleukin 4 ◽  
Infection Model ◽  
Granulocytic Ehrlichiosis ◽  
Human Granulocytic Ehrlichiosis ◽  
Ifn Γ ◽  
Immunocompetent Mice ◽  
Deficient Mice

ABSTRACT The cytokine response to the agent of human granulocytic ehrlichiosis (HGE) was assessed in a murine infection model and the role of gamma interferon (IFN-γ), a cytokine that is crucial for host defenses against intracellular pathogens, was investigated by using IFN-γ-deficient mice. The agent of HGE (aoHGE) is an obligate intracellular bacterium that survives within neutrophils: morulae (vacuoles containing HGE organisms) are evident in polymorphonuclear leukocytes of experimentally infected immunocompetent mice for 1 to 2 weeks. We now show that IFN-γ levels increase during early infection of C3H/HeN or C57BL/6 mice with HGE bacteria. Moreover, in response to aoHGE extracts or concanavalin A, splenocytes from ehrlichia-infected mice produced more IFN-γ and less interleukin-4 than controls, suggesting that aoHGE partially skewed the immune response towards a Th1 phenotype. Absolute concentration of morulae containing neutrophils in blood was 122 ± 22 cells/μl on day 8. The bacterial DNA burden was also highest on day 8 and then declined after IFN-γ levels peaked. In contrast, IFN-γ-deficient mice had a markedly elevated HGE bacteria burden with morulae concentration of 282 ± 48 cells/μl on day 5 (P = 0.004) and 242 ± 63 cells/μl on day 8 (P = 0.005). Rickettsemia resolved in immunocompetent and IFN-γ deficient mice after 2 weeks, while both the immunocompetent and the IFN-γ-deficient mice had increased serum antibodies against aoHGE antigens at this time point. These data demonstrate that the HGE agent elicits a prominent IFN-γ response in mice and that IFN-γ is important in controlling the degree of rickettsemia during the early phase of infection, while IFN-γ independent mechanisms play a role at later time points.

scholarly journals Defect of CARD9 Leads to Impaired Accumulation of Gamma Interferon-Producing Memory Phenotype T Cells in Lungs and Increased Susceptibility to Pulmonary Infection with Cryptococcus neoformans

2014 ◽  
Vol 82 (4) ◽  
pp. 1606-1615 ◽  
Author(s):  
Hideki Yamamoto ◽  
Yuri Nakamura ◽  
Ko Sato ◽  
Yurie Takahashi ◽  
Toshiki Nomura ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Cryptococcus Neoformans ◽  
Host Defense ◽  
Pulmonary Infection ◽  
Gamma Interferon ◽  
Content Type ◽  
Memory Phenotype ◽  
Ifn Γ

ABSTRACTCaspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule signal that is critical for NF-κB activation and is triggered through C-type lectin receptors (CLRs), which are pattern recognition receptors that recognize carbohydrate structures. Previous studies have reported thatCryptococcus neoformans, a fungal pathogen that causes meningoencephalitis in AIDS patients, is recognized through some CLRs, such as mannose receptors or DC-SIGN. However, the role of CARD9 in the host defense against cryptococcal infection remains to be elucidated. In the present study, we analyzed the role of CARD9 in the host defense against pulmonary infection withC. neoformans. CARD9 gene-disrupted (knockout [KO]) mice were highly susceptible to this infection, as shown by the reduced fungal clearance in the infected lungs of CARD9 KO mice, compared to that in wild-type (WT) mice. Gamma interferon (IFN-γ) production was strongly reduced in CARD9 KO mice during the innate-immunity phase of infection. Reduced IFN-γ synthesis was due to impaired accumulation of NK and memory phenotype T cells, which are major sources of IFN-γ innate-immunity-phase production; a reduction in the accumulation of these cells was correlated with reduced CCL4, CCL5, CXCL9, and CXCL10 synthesis. However, differentiation of Th17 cells, but not of Th1 cells, was impaired at the adaptive-immunity phase in CARD9 KO mice compared to WT mice, although there was no significant difference in the infection susceptibility between interleukin 17A (IL-17A) KO and WT mice. These results suggest that CARD9 KO mice are susceptible toC. neoformansinfection probably due to the reduced accumulation of IFN-γ-expressing NK and memory phenotype T cells at the early stage of infection.

scholarly journals Role of Interleukin-18 in Host Defense against Disseminated Candida albicans Infection

2002 ◽  
Vol 70 (6) ◽  
pp. 3284-3286 ◽  
Author(s):  
Rogier J. L. Stuyt ◽  
Mihai G. Netea ◽  
Ineke Verschueren ◽  
Giamila Fantuzzi ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Protective Effect ◽  
Host Defense ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Ifn Γ ◽  
Candida Albicans Infection ◽  
Deficient Mice

ABSTRACT In mice injected intravenously with Candida albicans, administration of anti-interleukin-18 (IL-18) antibodies increased the yeast load in the kidneys. There was no effect on the organ load with Candida when gamma interferon (IFN-γ)-deficient mice were treated with anti-IL-18 antibodies, suggesting that the protective effect of IL-18 is mediated through endogenous IFN-γ.

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