Faculty Opinions recommendation of Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain.

2007 ◽  
Author(s):  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Gamma Interferon

scholarly journals Prior Exposure to Live Mycobacterium bovis BCG Decreases Cryptococcus neoformans-Induced Lung Eosinophilia in a Gamma Interferon-Dependent Manner

2003 ◽  
Vol 71 (6) ◽  
pp. 3384-3391 ◽  
Author(s):  
Gerhard Walzl ◽  
Ian R. Humphreys ◽  
Ben G. Marshall ◽  
Lorna Edwards ◽  
Peter J. M. Openshaw ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Mycobacterium Bovis ◽  
Mycobacterial Infection ◽  
Gamma Interferon ◽  
Delayed Type Hypersensitivity ◽  
Infection Model ◽  
Dependent Manner ◽  
Interleukin 5 ◽  
Lung Eosinophilia ◽  
Mycobacterial Antigens

ABSTRACT Some common childhood infections appear to prevent the development of atopy and asthma. In some Mycobacterium bovis BCG-vaccinated populations, strong delayed-type hypersensitivity responses to mycobacterial antigens are associated with a reduced risk of atopy. Although BCG exposure decreases allergen-induced lung eosinophilia in animal models, little attention has been given to the effect of immunity to BCG on responses against live pathogens. We used the murine Cryptococcus neoformans infection model to investigate whether prior BCG infection can alter such responses. The present study shows that persistent pulmonary BCG infection of C57BL/6 mice induced an increase in gamma interferon, a reduction in interleukin-5, and a decrease in lung eosinophilia during subsequent Cryptococcus infection. This effect was long lasting, depended on the presence of live bacteria, and required persistence of mycobacterial infection in the lung. Reduction of eosinophilia was less prominent after infection with a mutant BCG strain (ΔhspR), which was rapidly cleared from the lungs. These observations have important implications for the development of vaccines designed to prevent Th2-mediated disease and indicate that prior lung BCG vaccination can alter the pattern of subsequent host inflammation.

scholarly journals Protection against Cryptococcosis by Using a Murine Gamma Interferon-Producing Cryptococcus neoformans Strain

2007 ◽  
Vol 75 (3) ◽  
pp. 1453-1462 ◽  
Author(s):  
Floyd L. Wormley ◽  
John R. Perfect ◽  
Chad Steele ◽  
Gary M. Cox
Keyword(s):  
Immune Responses ◽  
Cryptococcus Neoformans ◽  
Pulmonary Infection ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Host Immunity ◽  
Wild Type ◽  
Novel Method ◽  
Ifn Γ ◽  
Stimulation Of

ABSTRACT We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-γ). Mice given a pulmonary infection with an IFN-γ-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-γ-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-γ-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-γ results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.

scholarly journals Induction of T Helper Type 1 Responses by a Polysaccharide Deacetylase from Cryptococcus neoformans

2003 ◽  
Vol 71 (9) ◽  
pp. 5412-5417 ◽  
Author(s):  
Carmelo Biondo ◽  
Concetta Beninati ◽  
Mauro Bombaci ◽  
Luciano Messina ◽  
Giuseppe Mancuso ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cryptococcus Neoformans ◽  
Interleukin 2 ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
T Helper ◽  
Spleen Cells ◽  
Induce Cell Proliferation ◽  
Helper Type

ABSTRACT A 25-kDa cryptococcal deacetylase (d25) was found here to induce cell proliferation, as well as secretion of interleukin 2 and gamma interferon, but not interleukin 4, in spleen cells from d25-immunized or Cryptococcus neoformans-infected mice. The gamma interferon, but not the interleukin 2, response was required for the protective activities of d25 immunization in a murine cryptococcosis model.

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 The Gamma Interferon Receptor Is Required for the Protective Pulmonary Inflammatory Response to Cryptococcus neoformans

2005 ◽  
Vol 73 (3) ◽  
pp. 1788-1796 ◽  
Author(s):  
Gwo-Hsiao Chen ◽  
Roderick A. McDonald ◽  
Jason C. Wells ◽  
Gary B. Huffnagle ◽  
Nicholas W. Lukacs ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Receptor Gene ◽  
Inflammatory Cells ◽  
Gamma Interferon ◽  
Pulmonary Cryptococcosis ◽  
Cryptococcal Infection ◽  
Pulmonary Inflammatory Response ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Mice with a null deletion mutation in the gamma interferon (IFN-γ) receptor gene were used to study the role of IFN-γ responsiveness during experimental pulmonary cryptococcosis. Cryptococcus neoformans was inoculated intratracheally into mice lacking the IFN-γ receptor gene (IFN-γR−/−) and into control mice (IFN-γR+/+). The numbers of CFU in lung, spleen, and brain were determined to assess clearance; cytokines produced by lung leukocytes were measured, and survival curves were generated. In the present study, we demonstrate the following points. (i) IFN-γR−/− mice are markedly more susceptible to C. neoformans infection than IFN-γR+/+ mice. (ii) In the absence of IFN-γ signaling, pulmonary CFU continue to increase over the course of infection, and the infection disseminates to the brain. (iii) In the absence of IFN-γ receptor, recruitment of inflammatory cells in response to pulmonary cryptococcal infection is not impaired. (iv) At week 5 postinfection, IFN-γR−/− mice have recruited greater numbers of leukocytes into their lungs, with neutrophils, eosinophils, and lymphocytes accounting for this cellular increase. (v) IFN-γ signaling is required for the development of a T1 over a T2 immune response in the lung following cryptococcal infection. These results indicate that in the absence of IFN- γ responsiveness, even though the recruitment of pulmonary inflammatory cells is not impaired and the secretion of IFN-γ is not affected, IFN-γR−/− mice do not have the ability to resolve the cryptococcal infection. In conclusion, our data suggest that proper functional IFN-γ signaling, possibly through a mechanism which inhibits the potentially disease-promoting T2 response, is required for mice to confine the cryptococcal infection.

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