Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first international meeting on endemic mycoses of the Americas (IMEMA)

Background: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. Objectives: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). Methods: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. Results: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1–3)-β-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. Conclusions: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.Fil: Caceres, Diego H.. Universidad Colegio Mayor de Nuestra Señora del Rosario; Colombia. Centers for Disease Control and Prevention; Estados UnidosFil: Echeverri Tirado, Laura C.. Universidad de Antioquia; ColombiaFil: Bonifaz, Alexandro. Hospital General de Mexico; MéxicoFil: Adenis, Antoine. Inserm; FranciaFil: Gomez, Beatriz L.. Universidad Colegio Mayor de Nuestra Señora del Rosario; ColombiaFil: Bnada Flores, Claudia Lizett. Universidad Peruana Cayetano Heredia; PerúFil: Canteros, Cristina Elena. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Santos, Daniel Wagner. Universidade Federal do Maranhao; BrasilFil: Arathoon, Eduardo. Asociación de Salud Integral; GuatemalaFil: Ramirez Soto, Elia. Centro Nacional de Enfermedades Tropicales; BoliviaFil: Queiroz-Telles, Flavio. Universidade Federal do Paraná; BrasilFil: Schwartz, Ilan S.. University of Alberta; CanadáFil: Zurita, Jeannete. Pontificia Universidad Católica del Ecuador; EcuadorFil: Serra Damasceno, Lisandra. Universidade Estadual do Ceará; BrasilFil: Garcia, Nataly. Sociedad Venezolana de Microbiología; VenezuelaFil: Fernandez, Norma B.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Chincha, Omayra. Universidad Peruana Cayetano Heredia; PerúFil: Araujo, Patricia. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Rabagliati, Ricardo. No especifíca;Fil: Chiller, Tom. Centers for Disease Control and Prevention; Estados UnidosFil: Giusiano, Gustavo Emilio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

PARP-1 is critical for recruitment of dendritic cells to the lung in a mouse model of asthma but dispensable for their differentiation and function

Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear. In this study, we examined whether PARP-1 is critical for DC differentiation and function using bone marrow progenitors and their migration to the lung in an ovalbumin-based mouse model of asthma. Results show that changes in PARP-1 levels during GM-CSF-induced DC differentiation from bone marrow progenitors were cyclic and appear to be part of an array of changes that included STAT3/STAT5/STAT6/GRAIL/RAD51. Interestingly, PARP-1 gene deletion affected primarily STAT6 and γH2AX. PARP-1 inhibition significantly reduced the migration of DCs to the lungs of ovalbumin-challenged mice, which was associated with a concomitant reduction in lung levels of the adhesion molecule VCAM-1. The requirement of PARP-1 for VCAM-1 expression was confirmed using endothelial and lung smooth muscle cells. PARP-1 expression and activity were also required for VCAM-1 in differentiated DCs. An assessment of CD11b+/CD11c+/MHCIIhigh DCs in spleens and lymph nodes of OVA-sensitized mice revealed that PARP-1 inhibition genetically or by olaparib exerted little to no effect on DC differentiation, percentage of CD80+/CD86+/CD40+-expressing cells, or their capacity to promote proliferation of ovalbumin-primed (OTII) CD4+ T cells. These findings were corroborated using GM-CSF-induced differentiation of DCs from the bone marrow. Surprisingly, the PARP-1-/- DCs exhibited a higher intrinsic capacity to induce OTII CD4+ T cell proliferation in the absence of ovalbumin. Overall, our results show that PARP-1 plays little to no role in DC differentiation and function and that the protective effect of PARP-1 inhibition against asthma is associated with a prevention of DC migration to the lung through a reduction in VCAM-1 expression. Given the current use of PARP inhibitors (e.g., olaparib) in the clinic, the present results may be of interest for the relevant therapies