[44] On the other hand, very aggressive EAE induction (for example, repeated immunization with high dosages of heat-killed Mtb) completely abrogates IFN-β efficacy Cobimetinib in wild-type mice (Inoue et al., unpublished data). Hence, EAE induced by moderately aggressive immunization may develop as a mixture of two EAE subtypes; NLRP3 inflammasome-dependent and -independent. When two subtypes of EAE are ongoing, it may be possible that IFN-β efficacy correlates with levels

of NLRP3 inflammasome dependency in EAE development. Although two subtypes of EAE may be occurring simultaneously within some of the disease in WT mice, the findings are summarized as follows: NLRP3 inflammasome-dependent EAE is a disease that responds to IFN-β treatment, whereas NLRP3 inflammasome-independent EAE is a disease that is resistant to IFN-β (Fig. 2). Previous studies have shown that passive EAE induced by Th17 cell transfer is resistant to IFN-β treatment, whereas the disease induced by Th1 cells responds to IFN-β treatment.[81] The result is counterintuitive because IFN-β inhibits Th17 responses;[62, 65] and it will be of great interest to understand why Th17-mediated EAE cannot be treated by IFN-β. Activation status of the NLRP3 inflammasome is not known in the Th17-mediated EAE model, but the result (resistance of Th17-mediated passive EAE to IFN-β) does not conflict with IFN-β resistance in NLRP3 inflammasome-independent

EAE. This is because the Th17 response itself is not the reason

for NLRP3 inflammasome-dependent EAE progression.[44] Further studies will be necessary to determine whether or not these two types BGB324 of IFN-β-resistant EAE (Th17-type EAE and NLRP3 inflammasome-independent Cell press EAE) share the same mechanism. It is currently unknown whether NLRP3 inflammasome-independent MS exists. It is also not known what type of event is an equivalent of ‘aggressive immunization’ in MS. However, if the current findings on the correlation between NLRP3 inflammasome activation and response to IFN-β in EAE can be applied to MS, it might be possible to predict MS patients who do not respond well to IFN-β therapy. For example, the activation status of the NLRP3 inflammasome might be a prediction marker. Or, it might be possible to identify prediction markers by screening molecules that show altered expression in NLRP3 inflammasome-independent EAE. It is also possible to test such molecules for prognosis markers, or even as molecular targets of selected treatment(s). “
“Human Vγ9Vδ2 T cells play a crucial role in early immune response to intracellular pathogens. Their number is drastically increased in the peripheral blood of patients during the acute phase of brucellosis. In vitro, Vγ9Vδ2 T cells exhibit strong cytolytic activity against Brucella-infected cells and impair intracellular growth of Brucella suis in autologous macrophages.