Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Transplante lobar experimental em suínos: enxerto proporcional na disparidade entre receptor e doador Experimental lobar transplantation in swine: proportional graft in the discrepancy between donor and recipient

Objetivo - Perante a crítica falta de orgãos disponíveis para transplante, a doação intervivos de lobos ou segmentos pulmonares é possível e necessária no transplante pulmonar pediátrico. Na grande disparidade de tamanho do doador adulto e a criança pequena receptora, o lobo médio ou segmento pulmonar representa um enxerto de restrito leito vascular. Este estudo experimental testa a hipótese de que esse tipo de enxerto pode desenvolver hipertensão pulmonar no animal receptor, ao final do período de crescimento. Métodos - Foi utilizado um modelo de sobrevivência de transplante pulmonar à esquerda em leitões. Constituíram-se três grupos de comparação: I (n = 4) - transplante de lobo superior de doador adulto, enxerto proporcional ao receptor, mas irrigado por apenas dois ramos arteriais; II (n = 5) - transplante de lobo inferior de doador adulto, enxerto desproporcional ao receptor e com amplo leito vascular; III (n = 6) - transplante de pulmão imaturo de leitão doador proporcionado. Os animais transplantados tiveram a função do enxerto pulmonar estudada ao final de 3 meses, quando completaram o período de crescimento. Resultados - A pressão da artéria pulmonar do enxerto do grupo I (51,8 ± 2,1mmHg) foi mais elevada do que no grupo II (40,4 ± 2,5mmHg) e do que no grupo III (34,8 ± 1,5mmHg), atingindo significância estatística (p = 0,0003). Conclusões - O enxerto lobar proporcional ao receptor, mas de leito vascular restrito, teve desempenho hemodinâmico comprometido no animal em crescimento. Esses dados sugerem que a proporcionalidade do enxerto não deve ser prioritária e, antes, ser secundária a um adequado leito vascular do enxerto.<br>Background - The critical donor shortage in pediatric pulmonary transplantation has prompted lobar transplantation from living-related. However, in the case of great size discrepancy between the adult donor and the small child recipient, a pulmonary segment or medium lobe represents grafts with restricted vascular bed. The authors hypothesized that this type of graft may develop pulmonary hypertension in the recipient by the end of the growth period. Methods - This hypothesis was investigated in a porcine survival model of lung transplantation in piglets. There were three groups for comparison purposes: I (n = 4) - transplantation of the upper lobe from an adult donor, graft being proportional to the recipient but irrigated by two arterial rami only; II (n = 5) - transplantation of the lower lobe from an adult donor, graft being oversized to the recipient and having adequate vascular bed; III (n = 6) - transplantation of immature lung, from matched-sized donor. Graft function was studied three months after the transplantation, when the growth period was completed. Results - The pulmonary artery pressure of grafts in group I (51.8 ± 2.1 mmHg) was increased compared to that of group II (40.4 ± 2.5 mmHg) and of group III (34.8 ± 1.5 mmHg), reaching statistical significance (p = 0.0003). Conclusions - The lobar graft proportional to the recipient, with restricted vascular bed, had hampered hemodynamic performance in the growing animal. These results suggest that graft proportionality should be secondary to an adequate vascular bed