scholarly journals Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

2001 ◽  
Vol 69 (2) ◽  
pp. 906-911 ◽  
Author(s):  
Abhay R. Satoskar ◽  
Marcelo Bozza ◽  
Miriam Rodriguez Sosa ◽  
Guoshing Lin ◽  
John R. David
Keyword(s):  
Migration Inhibitory Factor ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Wild Type ◽  
Leishmanicidal Activity ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF−/−) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF−/− mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF−/− mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-γ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-γ-activated resting peritoneal macrophages from MIF−/− mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF−/− mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. majorin vivo. Furthermore, they indicate that the susceptibility of MIF−/− mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

scholarly journals Macrophage Migration Inhibitory Factor Plays a Critical Role in Mediating Protection against the Helminth Parasite Taenia crassiceps

2003 ◽  
Vol 71 (3) ◽  
pp. 1247-1254 ◽  
Author(s):  
Miriam Rodríguez-Sosa ◽  
Lucia E. Rosas ◽  
John R. David ◽  
Rafael Bojalil ◽  
Abhay R. Satoskar ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Critical Role ◽  
Helminth Parasite ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Soluble Antigen ◽  
Necrosis Factor Alpha ◽  
Taenia Crassiceps ◽  
Ifn Γ

ABSTRACT To determine the role of endogenous migration inhibitory factor (MIF) in regulation of immune response during murine cysticercosis caused by the helminth parasite Taenia crassiceps, we analyzed the course of T. crassiceps infection in MIF−/− BALB/c mice. MIF−/− mice were highly susceptible to T. crassiceps and developed significantly higher parasite loads compared to similarly infected MIF+/+ mice. Throughout the course of infection, Taenia crassiceps soluble antigen-stimulated spleen cells from both MIF+/+ and MIF−/− mice produced significant and comparable levels of interleukin-4 (IL-4), but those from MIF−/− mice produced significantly more IL-13, as well as gamma interferon (IFN-γ), suggesting that the susceptibility of MIF−/− mice to T. crassiceps was not due to the lack of IFN-γ production. Interestingly, low levels of both total and specific immunoglobulin G2a were observed in MIF−/− cysticercotic mice despite the high IFN-γ levels; in addition, peritoneal macrophages obtained from T. crassiceps-infected MIF−/− mice at different time points failed to respond efficiently to stimulation in vitro with lipopolysaccharide plus IFN-γ and produced significantly lower levels of IL-12, tumor necrosis factor alpha, and NO compared to those from MIF+/+ mice. These findings demonstrate that MIF plays a critical role in mediating protection against T. crassiceps in vivo. Moreover, these findings also suggest that impaired macrophage function rather than the lack of Th1 development may be responsible for mediating susceptibility to T. crassiceps.

scholarly journals Toll-Like Receptor 2 Controls the Gamma Interferon Response to Francisella tularensis by Mouse Liver Lymphocytes

2007 ◽  
Vol 75 (11) ◽  
pp. 5338-5345 ◽  
Author(s):  
Kee-Jong Hong ◽  
Jason R. Wickstrum ◽  
Hung-Wen Yeh ◽  
Michael J. Parmely
Keyword(s):  
Francisella Tularensis ◽  
Cell Types ◽  
Gamma Interferon ◽  
Interferon Response ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT The production of gamma interferon (IFN-γ) is a key step in the protective innate immune response to Francisella tularensis. Natural killer cells and T cells in the liver are important sources of this cytokine during primary F. tularensis infections, and interleukin-12 (IL-12) appears to be an essential coactivating cytokine for hepatic IFN-γ expression. The present study was undertaken to determine whether or not macrophages (Mφ) or dendritic cells (DC) provide coactivating signals for the liver IFN-γ response in vitro, whether IL-12 mediates these effects, and whether Toll-like receptor (TLR) signaling is essential to induce this costimulatory activity. Both bone marrow-derived Mφ and DC significantly augmented the IFN-γ response of F. tularensis-challenged liver lymphocytes in vitro. While both cell types produced IL-12p40 in response to F. tularensis challenge, only DC secreted large quantities of IL-12p70. DC from both IL-12p35-deficient and TLR2-deficient mice failed to produce IL-12p70 and did not costimulate liver lymphocytes for IFN-γ production in response to viable F. tularensis organisms. Conversely, liver lymphocytes from TLR2-deficient mice cocultured with wild-type accessory cells produced IFN-γ at levels comparable to those for wild-type hepatic lymphocytes. These findings indicate that TLR2 controls hepatic lymphocyte IFN-γ responses to F. tularensis by regulating DC IL-12 production. While Mφ also coinduced hepatic IFN-γ production in response to F. tularensis, they did so in a fashion less dependent on TLR2.

scholarly journals Interleukin 10- and Fcγ Receptor-Deficient Mice Resolve Leishmania mexicana Lesions

2005 ◽  
Vol 73 (4) ◽  
pp. 2101-2108 ◽  
Author(s):  
Laurence U. Buxbaum ◽  
Phillip Scott
Keyword(s):  
Chronic Disease ◽  
Interleukin 10 ◽  
Delayed Type Hypersensitivity ◽  
Leishmania Mexicana ◽  
Wild Type ◽  
Enhanced Resistance ◽  
Lymph Node Cells ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10−/− (IL-10−/−) mice resolve their lesions and exhibit increased gamma interferon (IFN-γ), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment of L. mexicana-infected IL-10−/− mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonized L. mexicana induced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRγ−/− mice resolve L. mexicana lesions, and lymph node cells from these mice produced less IL-10 and more IFN-γ than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcγR leads to resolution of L. mexicana disease and support a model in which ligation of FcγR by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.

scholarly journals Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6981-6986 ◽  
Author(s):  
Mineo Watanabe ◽  
Masaaki Nagai
Keyword(s):  
Immune Response ◽  
Respiratory Infection ◽  
Murine Model ◽  
Protective Immunity ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
Bordetella Parapertussis ◽  
Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

scholarly journals Heterogeneity of Wild Leishmania major Isolates in Experimental Murine Pathogenicity and Specific Immune Response

2001 ◽  
Vol 69 (8) ◽  
pp. 4906-4915 ◽  
Author(s):  
C. Kébaı̈er ◽  
H. Louzir ◽  
M. Chenik ◽  
A. Ben Salah ◽  
K. Dellagi
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 4 ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Tunisian Patients ◽  
Ifn Γ

ABSTRACT Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 × 106 amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-γ) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-γ in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host.

scholarly journals Perforin and Gamma Interferon Expression Are Required for CD4+ and CD8+ T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination

2009 ◽  
Vol 77 (10) ◽  
pp. 4383-4395 ◽  
Author(s):  
Bruna C. G. de Alencar ◽  
Pedro M. Persechini ◽  
Filipe A. Haolla ◽  
Gabriel de Oliveira ◽  
Jaline C. Silverio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Plasmid Dna ◽  
Protective Immunity ◽  
Recombinant Adenovirus ◽  
Ifn Γ ◽  
Adenovirus 5 ◽  
Deficient Mice

ABSTRACT A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4+ and CD8+ T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4+ and CD8+ T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-γ) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8+ T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-γ or IFN-γ/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-γ in the presence of highly cytotoxic T cells. Vaccinated IFN-γ-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-γ in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.

IFN-γ deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet

2013 ◽  
Vol 305 (12) ◽  
pp. G891-G899 ◽  
Author(s):  
Xiao-Yu Luo ◽  
Terumi Takahara ◽  
Kengo Kawai ◽  
Masayuki Fujino ◽  
Toshiro Sugiyama ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Wild Type ◽  
High Fat ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Deficient Mice ◽  
Necrosis Factor

Cytokines play important roles in all stages of steatohepatitis, including hepatocyte injury, the inflammatory response, and the altered function of sinusoidal cells. This study examined the involvement of a major inflammatory cytokine, interferon-γ (IFN-γ), in the progression of steatohepatitis. In a steatohepatitis model by feeding a methionine- and choline-deficient high-fat (MCDHF) diet to both wild-type and IFN-γ-deficient mice, the liver histology, expression of genes encoding inflammatory cytokines, and fibrosis-related markers were examined. To analyze the effects of IFN-γ on Kupffer cells in vitro, we examined the tumor necrosis factor-α (TNF-α) production by a mouse macrophage cell line. Forty two days of MCDHF diet resulted in weight loss, elevated aminotransferases, liver steatosis, and inflammation in wild-type mice. However, the IFN-γ-deficient mice exhibited less extensive changes. RT-PCR revealed that the expression of tumor necrosis factor-α (TNF-α), transforming growth factor-β, inducible nitric oxide synthase, interleukin-4 and osteopontin were increased in wild-type mice, although they were suppressed in IFN-γ-deficient mice. Seventy days of MCDHF diet induced much more liver fibrosis in wild-type mice than in IFN-γ-deficient mice. The expression levels of fibrosis-related genes, α-smooth muscle actin, type I collagen, tissue inhibitor of matrix metalloproteinase-1, and matrix metalloproteinase-2, were dramatically increased in wild-type mice, whereas they were significantly suppressed in IFN-γ-deficient mice. Moreover, in vitro experiments showed that, when RAW 264.7 macrophages were treated with IFN-γ, they produced TNF-α in a dose-dependent manner. The present study showed that IFN-γ deficiency might inhibit the inflammatory response of macrophages cells and subsequently suppress stellate cell activation and liver fibrosis. These findings highlight the critical role of IFN-γ in the progression of steatohepatitis.

scholarly journals Endogenous Interleukin 4 Is Required for Development of Protective CD4+ T Helper Type 1 Cell Responses to Candida albicans

1998 ◽  
Vol 187 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Antonella Mencacci ◽  
Giuseppe Del Sero ◽  
Elio Cenci ◽  
Cristiana Fè d'Ostiani ◽  
Angela Bacci ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Early Stage ◽  
Interleukin 4 ◽  
T Helper ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Helper Type

Interleukin (IL)-4–deficient mice were used to assess susceptibility to systemic or gastrointestinal Candida albicans infections, as well as parameters of innate and elicited T helper immunity. In the early stage of systemic infection with virulent C. albicans, an unopposed interferon (IFN)-γ response renders IL-4–deficient mice more resistant than wild-type mice to infection. Yet, IL-4–deficient mice failed to efficiently control infection in the late stage and succumbed to it. Defective IFN-γ and IL-12 production, but not IL-12 responsiveness, was observed in IL-4–deficient mice that failed to mount protective T helper type 1 cell (Th1)-mediated acquired immunity in response to a live vaccine strain of the yeast or upon mucosal immunization in vivo. In vitro, IL-4 primed neutrophils for cytokine release, including IL-12. However, late treatment with exogenous IL-4, while improving the outcome of infection, potentiated CD4+ Th1 responses even in the absence of neutrophils. These findings indicate that endogenous IL-4 is required for the induction of CD4+ Th1 protective antifungal responses, possibly through the combined activity on cells of the innate and adaptive immune systems.

Ex vivoevidence for PGE2and LTB4involvement in cutaneous leishmaniasis: relation with infection status and cytokine production

Parasitology ◽  
1996 ◽  
Vol 112 (1) ◽  
pp. 13-19 ◽  
Author(s):  
S. Milano ◽  
F. Arcoleo ◽  
M. Dieli ◽  
R. D'agostino ◽  
G. De Nucci ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Ex Vivo ◽  
Early Stage ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Prostaglandin E ◽  
Ifn Γ

SUMMARYEx vivoculture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major(L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2(PGE2) and for leukotriene B4(LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected againstL. majorby sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and for the relative increase in the interleukin-4 (IL-4) became higher and higher as the lesion progressed. On the contrary, the cured mice produced levels of PGE2similar to normal uninfected controls, high levels of TNFα and IFN-γ and low levels of IL-4. Elevated levels of LTB4were detected in the early stage of infection in the unprotected mice compared to cured ones, a sign of more intense inflammation and a stimulus for the recruitment of inflammatory cells. The observation that exogenous LTB4was able to enhance in vitro both Th1cytokines in cured mice and Th2cytokines in unprotected ones suggests that LTB4could act in the recruitment of the T cells already committed to Th1or Th2phenotype.

Leishmania major H-line attenuated under pressure of gentamicin, induces a Th1 response which protects susceptible BALB/c mice against infection with virulent L. major

Parasitology ◽  
2009 ◽  
Vol 136 (11) ◽  
pp. 1243-1250 ◽  
Author(s):  
HAMID DANESHVAR ◽  
RICHARD BURCHMORE ◽  
PAUL HAGAN ◽  
R. STEPHEN PHILLIPS
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Cell Line ◽  
Leishmania Major ◽  
Wild Type ◽  
Th1 Response ◽  
Th2 Responses ◽  
Draining Lymph Node ◽  
Ifn Γ

SUMMARYAn attenuated line of Leishmania major (L. major H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A modification of the previously described method for the generation of attenuated L. major is described, giving rise to attenuated parasites after 8 rather than 12 subpassages. No lesions developed in BALB/c mice infected with L. major H-line, whereas L. major wild-type (WT) induced a Th2 like response with progressive lesions. Analysis of splenocyte IFN-γ and IL-4 production following stimulation with promastigotes shows that the L. major H-line preferentially induces Th1-like responses and possibly down-regulates Th2 responses in BALB/c mice. L. major H-line parasites remained localized in the skin and draining lymph node, whereas L. major WT parasites disseminated into the visceral organs of BALB/c mice. Mice infected with L. major H-line acquired some resistance against L. major WT. These results show that the attenuated cell line of L. major is not only avirulent but that it may also modulate the host immune response.

Sign in / Sign up

Export Citation Format

Share Document