PMC:4503824 / 39756-42322 JSONTXT

{"project":"2_test","denotations":[{"id":"25498576-19893050-43267851","span":{"begin":746,"end":750},"obj":"19893050"},{"id":"25498576-21359196-43267852","span":{"begin":1095,"end":1099},"obj":"21359196"},{"id":"25498576-23894196-43267853","span":{"begin":1705,"end":1709},"obj":"23894196"},{"id":"25498576-17911623-43267854","span":{"begin":1816,"end":1820},"obj":"17911623"},{"id":"25498576-19752036-43267855","span":{"begin":1930,"end":1934},"obj":"19752036"},{"id":"25498576-19893050-43267856","span":{"begin":2219,"end":2223},"obj":"19893050"}],"text":"The host T helper subset and associated cytokines are important in the progression and outcome of cryptococcal infection with Th1 and Th17 profiles associated with clearance of cryptococcal infection, and Th2 profiles associated with cryptococcal dissemination and host damage. A preferential Th1/Th17 response in comparison to a Th2 response was shown using an IL 4/IL 13 double knockout murine model. These mice generated a Th1/Th17 response in leukocytes and pulmonary lymph nodes against cryptococcal infection, in comparison to wild type mice that generated a Th2 profile. The Th1/Th17 response was shown to be less damaging to the host through reduced fungal burden, no eosinophilia or airway damage and no systemic IgE load (Zhang et al., 2009). Thus, it appears that generation of a Th2 response from cryptococcal challenge is detrimental to the host, whilst a Th1/Th17 profile is beneficial. Interestingly, in response to IFNγ producing C. neoformans, IL 17A is secreted primarily from neutrophils in mice, and may be helpful in the clearance of cryptococcal infection (Wozniak et al., 2011). Similarly, using a murine model, IL 13 a Th2 cytokine, is shown to be detrimental for the host during cryptococcal infection. Overexpressing IL 13 mice were more susceptible to infection, through creation of a Th2 profile whilst inhibiting IL 17 production. IL 33 receptor deficient mice had better survival and reduced fungal burden in comparison to wild types. Using this mouse model, IL-33 was shown to be involved in the induction of type 2 lymphoid cells, alternatively activated macrophages and the associated Th2 profile, leading to a better environment for virulent cryptococci (Flaczyk et al., 2013). Subsequent recruitment of eosinophils and airway inflammation were damaging to the host (Muller et al., 2007). Damage to airways is shown to occur in Th2 profiles and is correlated with production of IgE (Jain et al., 2009). This indicates that Th2 host damage may in part be caused by an allergic response. However, Th1/Th17 profiles are not sufficient to stop cryptococcal dissemination, as IL 14/IL 13 knockout mice, which do not develop Th2 profile, were not protected from dissemination (Zhang et al., 2009). Therefore, at the level of T cell profiling there is a clear and consistent separation in requirements in pro inflammatory pathways. However, greater detail in the positive roles of Th2 responses in resolution of inflammation in cryptococcal infection and the timing of the requirements of the different T helper elements in still required."}