PMC:4503824 / 48418-51987 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4503824","sourcedb":"PMC","sourceid":"4503824","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4503824","text":"13 The immune response to C. gattii\nAs the major disease causing organism most studies have focussed on C. neoformans. We know that C. gattii is able to infect those with apparently normal immune systems suggesting that there must be large differences in the immune response to this species. One intriguing difference is that C. gattii generally has a reduced ability to grow within macrophages than C. neoformans (Voelz et al., 2014). The exception is the hyper proliferative genotypes isolated from the Vancouver Island Outbreak (VIO; (Ma et al., 2009)) and elsewhere in North America (Byrnes et al., 2010; Springer et al., 2014). These hyper proliferative strains show changes in mitochondrial gene expression and have a tubular mitochondria phenotype that closely correlates with macrophage parasitism and virulence in a mouse model (Ma et al., 2009). Recently, this has been shown to be dependent on the reactive oxygen species (ROS) response of host macrophages (May and Voelz, seminar presentation 8.4, ICCC9; Voelz et al., 2014). Inhibition of ROS production in macrophages was sufficient to block the increased intracellular proliferation of the VIO strains i.e. a host antimicrobial response is required for maximal virulence of the pathogen. How these strains are better able to proliferate in macrophages is unclear but this is a phenomenon that appears to function through modulating the host phagosome, since coinfection of hyper and hypo proliferative strains together leads to a hyper proliferation phenotype conferred to both infecting strains.\nThe primary immune response to C. gattii is still unclear with both a hyper and hypo inflammatory response reported and there is some evidence from mouse models that C. gattii may more readily cause pulmonary infection than spread to the CNS (Ngamskulrungroj et al., 2012). In vitro stimulation of monocytes demonstrated higher levels of inflammatory cytokines, while the pulmonary immune response to a VIO strain was poor in comparison to a non VIO and to a C. neoformans strain when assessed by histology (Okubo et al., 2013). Fewer Th1/Th17 lymphocytes are present in the lungs of C. gattii infected mice (Angkasekwinai et al., 2014) and there is reduced levels neutrophil infiltration in comparison to C. neoformans infection (Cheng et al., 2009). However, immunisation with C. gattii cell wall or cytoplasmic components can confer a protective response to subsequent C. gattii infection (Chaturvedi et al., 2014).\nMice deficient in C1q or C3 or depletion of complement with cobra venom factor showed overwhelming lung fungal burden after infection with C. gattii (Mershon et al., 2009). C. gattii is a able to disrupt dendritic cell maturation by blocking TNFα release (Huston et al., 2013). In this case DCs are not activated and this leads to subsequent non activation of further TNFα secretion, antigen presentation and reduced T lymphocyte proliferation. This is further supported with TNFα induction or addition of exogenous TNFα restoring DC functions. The resulting absence of adaptive response may therefore enable infection within immune competent hosts by C. gattii (Huston et al., 2013). Finally, it is important to note that there may be cryptic immune pathology in those that are infected with C. gattii. A recent study has also identified GMCSF autoantibodies as a risk factor for C. gattii and this highlights that further work is needed to understand differences in both host and pathogen in C. gattii infection (Kwon-Chung et al., seminar presentation 5.1, ICCC9; Saijo et al., 2014).","divisions":[{"label":"label","span":{"begin":0,"end":2}},{"label":"title","span":{"begin":4,"end":36}},{"label":"p","span":{"begin":37,"end":1562}},{"label":"p","span":{"begin":1563,"end":2481}}],"tracks":[{"project":"2_test","denotations":[{"id":"25498576-25323068-43267871","span":{"begin":430,"end":434},"obj":"25323068"},{"id":"25498576-19651610-43267872","span":{"begin":550,"end":554},"obj":"19651610"},{"id":"25498576-20421942-43267873","span":{"begin":627,"end":631},"obj":"20421942"},{"id":"25498576-25144534-43267873","span":{"begin":627,"end":631},"obj":"25144534"},{"id":"25498576-19651610-43267874","span":{"begin":850,"end":854},"obj":"19651610"},{"id":"25498576-25323068-43267875","span":{"begin":1032,"end":1036},"obj":"25323068"},{"id":"25498576-22570277-43267876","span":{"begin":1830,"end":1834},"obj":"22570277"},{"id":"25498576-23698482-43267877","span":{"begin":2085,"end":2089},"obj":"23698482"},{"id":"25498576-24980974-43267878","span":{"begin":2194,"end":2198},"obj":"24980974"},{"id":"25498576-19635827-43267879","span":{"begin":2308,"end":2312},"obj":"19635827"},{"id":"25498576-25119981-43267880","span":{"begin":2475,"end":2479},"obj":"25119981"},{"id":"25498576-19114546-43267881","span":{"begin":2648,"end":2652},"obj":"19114546"},{"id":"25498576-23740956-43267882","span":{"begin":2753,"end":2757},"obj":"23740956"},{"id":"25498576-23740956-43267883","span":{"begin":3160,"end":3164},"obj":"23740956"}],"attributes":[{"subj":"25498576-25323068-43267871","pred":"source","obj":"2_test"},{"subj":"25498576-19651610-43267872","pred":"source","obj":"2_test"},{"subj":"25498576-20421942-43267873","pred":"source","obj":"2_test"},{"subj":"25498576-25144534-43267873","pred":"source","obj":"2_test"},{"subj":"25498576-19651610-43267874","pred":"source","obj":"2_test"},{"subj":"25498576-25323068-43267875","pred":"source","obj":"2_test"},{"subj":"25498576-22570277-43267876","pred":"source","obj":"2_test"},{"subj":"25498576-23698482-43267877","pred":"source","obj":"2_test"},{"subj":"25498576-24980974-43267878","pred":"source","obj":"2_test"},{"subj":"25498576-19635827-43267879","pred":"source","obj":"2_test"},{"subj":"25498576-25119981-43267880","pred":"source","obj":"2_test"},{"subj":"25498576-19114546-43267881","pred":"source","obj":"2_test"},{"subj":"25498576-23740956-43267882","pred":"source","obj":"2_test"},{"subj":"25498576-23740956-43267883","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93a5ec","default":true}]}]}}