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Find video protocols related to scientific articles indexed in Pubmed.
CD4(+) FoxP3(+) regulatory T cells suppress fatal T helper 2 cell immunity during pulmonary fungal infection.
Eur. J. Immunol.
PUBLISHED: 09-03-2014
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The opportunistic fungal pathogen Cryptococcus neoformans causes lung inflammation and fatal meningitis in immunocompromised patients. Regulatory T (Treg) cells play an important role in controlling immunity and homeostasis. However, their functional role during fungal infection is largely unknown. In this study, we investigated the role of Treg cells during experimental murine pulmonary C. neoformans infection. We show that the number of CD4(+) FoxP3(+) Treg cells in the lung increases significantly within the first 4 weeks after intranasal infection of BALB/c wild-type mice. To define the function of Treg cells we used DEREG mice allowing selective depletion of CD4(+) FoxP3(+) Treg cells by application of diphtheria toxin. In Treg cell-depleted mice, stronger pulmonary allergic inflammation with enhanced mucus production and pronounced eosinophilia, increased IgE production, and elevated fungal lung burden were found. This was accompanied by higher frequencies of GATA-3(+) T helper (Th) 2 cells with elevated capacity to produce interleukin (IL)-4, IL-5, and IL-13. In contrast, only a mild increase in the Th1-associated immune response unrelated to the fungal infection was observed. In conclusion, the data demonstrate that during fungal infection pulmonary Treg cells are induced and preferentially suppress Th2 cells thereby mediating enhanced fungal control.
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AIDS-related mycoses: the way forward.
Trends Microbiol.
PUBLISHED: 03-04-2014
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The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.
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IL-4 receptor-alpha-dependent control of Cryptococcus neoformans in the early phase of pulmonary infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. Previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (IL)-4R?-dependent type 2 immune responses, whereas IL-12-dependent type 1 responses confer resistance. In the experiments presented here, IL-4R??/? mice unexpectedly show decreased fungal control early upon infection with C. neoformans, whereas wild-type mice are able to control fungal growth accompanied by enhanced macrophage and dendritic cell recruitment to the site of infection. Lower pulmonary recruitment of macrophages and dendritic cells in IL-4R??/? mice is associated with reduced pulmonary expression of CCL2 and CCL20 chemokines. Moreover, IFN-? and nitric oxide production are diminished in IL-4R??/? mice compared to wild-type mice. To directly study the potential mechanism(s) responsible for reduced production of IFN-?, conventional dendritic cells were stimulated with C. neoformans in the presence of IL-4 which results in increased IL-12 production and reduced IL-10 production. Together, a beneficial role of early IL-4R? signaling is demonstrated in pulmonary cryptococcosis, which contrasts with the well-known IL-4R?-mediated detrimental effects in the late phase.
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Abrogation of IL-4 receptor-?-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response.
Int. Immunol.
PUBLISHED: 03-26-2013
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In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor ? (IL-4R?)-dependent polyfunctional T(h)2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4R?-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4R? expression on macrophages (LysM(Cre)IL-4R?(-/lox) mice) and IL-4R?(-/lox) littermates. LysM(Cre)IL-4R?(-/lox) mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysM(Cre)IL-4R?(-/lox) mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysM(Cre)IL-4R?(-/lox) and IL-4R?(-/lox) control mice, but macrophages from LysM(Cre)IL-4R?(-/lox) mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary T(h)2 responses were similar in infected LysM(Cre)IL-4R?(-/lox) and IL-4R?(-/lox) mice with each mouse strain harboring polyfunctional T(h)2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysM(Cre)IL-4R?(-/lox) and IL-4R?(-/lox) mice. Our results demonstrate that, despite residual IL-4R?-independent alternative macrophage activation and ongoing T(h)2-dependent allergic inflammation, abrogation of IL-4R?-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4R?(+/-) background indicating a key contribution of macrophage IL-4R? expression to susceptibility in allergic bronchopulmonary mycosis.
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Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis.
Am. J. Pathol.
PUBLISHED: 01-25-2011
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Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ?dblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ?dblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.