tetano
Editor, Senior Moderator
JCI Insight. 2017 Jan 26;2(2):e88257. doi: 10.1172/jci.insight.88257.
[h=1]Influenza A induces dysfunctional immunity and death in MeCP2-overexpressing mice.[/h] Cronk JC[SUP]1[/SUP], Herz J[SUP]2[/SUP], Kim TS[SUP]3[/SUP], Louveau A[SUP]2[/SUP], Moser EK[SUP]4[/SUP], Sharma AK[SUP]5[/SUP], Smirnov I[SUP]2[/SUP], Tung KS[SUP]6[/SUP], Braciale TJ[SUP]7[/SUP], Kipnis J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Loss of function or overexpression of methyl-CpG-binding protein 2 (MeCP2) results in the severe neurodevelopmental disorders Rett syndrome and MeCP2 duplication syndrome, respectively. MeCP2 plays a critical role in neuronal function and the function of cells throughout the body. It has been previously demonstrated that MeCP2 regulates T cell function and macrophage response to multiple stimuli, and that immune-mediated rescue imparts significant benefit in Mecp2-null mice. Unlike Rett syndrome, MeCP2 duplication syndrome results in chronic, severe respiratory infections, which represent a significant cause of patient morbidity and mortality. Here, we demonstrate that MeCP2[SUP]Tg3[/SUP] mice, which overexpress MeCP2 at levels 3- to 5-fold higher than normal, are hypersensitive to influenza A/PR/8/34 infection. Prior to death, MeCP2[SUP]Tg3[/SUP] mice experienced a host of complications during infection, including neutrophilia, increased cytokine production, excessive corticosterone levels, defective adaptive immunity, and vascular pathology characterized by impaired perfusion and pulmonary hemorrhage. Importantly, we found that radioresistant cells are essential to infection-related death after bone marrow transplantation. In all, these results demonstrate that influenza A infection in MeCP2[SUP]Tg3[/SUP] mice results in pathology affecting both immune and nonhematopoietic cells, suggesting that failure to effectively respond and clear viral respiratory infection has a complex, multicompartment etiology in the context of MeCP2 overexpression.
PMID: 28138553 DOI: 10.1172/jci.insight.88257
[PubMed - in process]
[h=1]Influenza A induces dysfunctional immunity and death in MeCP2-overexpressing mice.[/h] Cronk JC[SUP]1[/SUP], Herz J[SUP]2[/SUP], Kim TS[SUP]3[/SUP], Louveau A[SUP]2[/SUP], Moser EK[SUP]4[/SUP], Sharma AK[SUP]5[/SUP], Smirnov I[SUP]2[/SUP], Tung KS[SUP]6[/SUP], Braciale TJ[SUP]7[/SUP], Kipnis J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Loss of function or overexpression of methyl-CpG-binding protein 2 (MeCP2) results in the severe neurodevelopmental disorders Rett syndrome and MeCP2 duplication syndrome, respectively. MeCP2 plays a critical role in neuronal function and the function of cells throughout the body. It has been previously demonstrated that MeCP2 regulates T cell function and macrophage response to multiple stimuli, and that immune-mediated rescue imparts significant benefit in Mecp2-null mice. Unlike Rett syndrome, MeCP2 duplication syndrome results in chronic, severe respiratory infections, which represent a significant cause of patient morbidity and mortality. Here, we demonstrate that MeCP2[SUP]Tg3[/SUP] mice, which overexpress MeCP2 at levels 3- to 5-fold higher than normal, are hypersensitive to influenza A/PR/8/34 infection. Prior to death, MeCP2[SUP]Tg3[/SUP] mice experienced a host of complications during infection, including neutrophilia, increased cytokine production, excessive corticosterone levels, defective adaptive immunity, and vascular pathology characterized by impaired perfusion and pulmonary hemorrhage. Importantly, we found that radioresistant cells are essential to infection-related death after bone marrow transplantation. In all, these results demonstrate that influenza A infection in MeCP2[SUP]Tg3[/SUP] mice results in pathology affecting both immune and nonhematopoietic cells, suggesting that failure to effectively respond and clear viral respiratory infection has a complex, multicompartment etiology in the context of MeCP2 overexpression.
PMID: 28138553 DOI: 10.1172/jci.insight.88257
[PubMed - in process]