Cellular Inhibitor of Apoptosis Protein cIAP2 Protects against Pulmonary Tissue Necrosis during Influenza Virus Infection to Promote Host Survival

Rodrigue-Gervais, Ian Gaël; Labbé, Katherine; Dagenais, Maryse; Dupaul-Chicoine, Jeremy; Champagne, Claudia; Morizot, Alexandre; Skeldon, Alexander; Brincks, Erik L.; Vidal, Silvia M.; Griffith, Thomas S.; Saleh, Maya

doi:10.1016/j.chom.2013.12.003

Cited by 147 publications

(167 citation statements)

References 55 publications

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“…In support of this notion is the finding that deletion of the RIP kinase 3 (RIPK3) gene, a master regulator of programmed cell death by necroptosis 99 , is sufficient per se to confer tissue damage control and disease tolerance to systemic polymicrobial infection in mice 100 . Moreover, deletion of the Birc3 (cIAP2) gene, encoding a E3 ubiquitin ligase that suppresses necroptosis, impairs tissue damage control and disease tolerance to influenza virus infection in mice 101 . These findings suggest that stress-and damage-responses conferring tissue damage control may target directly or indirectly the RIPK1/3-driven necroptosis signal transduction pathway to confer disease tolerance or resistance to infection, a hypothesis that remains to be tested.…”

Section: Boxmentioning

confidence: 99%

Tissue damage control in disease tolerance

Soares

Gozzelino

Weis

2014

Trends in Immunology

159

174

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The deposited article is a prost-print version.This publication hasn't any creative commons license associated.This deposit is composed by the main article, and it hasn't any supplementary materials associated.Immune-driven resistance mechanisms are the prevailing host defense strategy against infection. By contrast, disease tolerance mechanisms limit disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen load. We propose here that tissue damage control underlies many of the protective effects of disease tolerance. We explore the mechanisms of cellular adaptation that underlie tissue damage control in response to infection as well as sterile inflammation, integrating both stress and damage responses. Finally, we discuss the potential impact of targeting these mechanisms in the treatment of disease.Fundação para a Ciência e Tecnologia grants: (PTDC/SAU-TOX/116627/2010, HMSP-ICT/0022/2010, SFRH/BPD/44256/2008); European Commission 7th Framework grant: (ERC-2011-AdG. 294709-DAMAGECONTROL); Deutsche Forschungsgemeinschaft grant: (DFG WE 4971/3-1).info:eu-repo/semantics/publishedVersio

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Section: Boxmentioning

confidence: 99%

Tissue damage control in disease tolerance

Soares

Gozzelino

Weis

2014

Trends in Immunology

159

174

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“…There have been several recent studies demonstrating both cell-intrinsic and cellextrinsic mechanisms that are needed to maintain proper airway epithelial integrity. Mice lacking cellular inhibitor of apoptosis 2 (cIAP2) were recently shown to exhibit increased lethality after influenza A virus infection without any observed difference in virus burden or in the immune response to infection (63). Rather, these cIAP2 mice displayed increased necroptosis in the airway epithelium.…”

Section: Isg15mentioning

confidence: 99%

Novel Mode of ISG15-Mediated Protection against Influenza A Virus and Sendai Virus in Mice

Morales

Monte

Sun

et al. 2015

J Virol

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ISG15 is a diubiquitin-like modifier and one of the most rapidly induced genes upon type I interferon stimulation. Hundreds of host proteins and a number of viral proteins have been shown to be ISGylated, and understanding how these modifications affect the interferon response and virus replication has been of considerable interest. ISG15؊/؊ mice exhibit increased susceptibility to viral infection, and in the case of influenza B virus and vaccinia virus, ISG15 conjugation has been shown to restrict virus replication in vivo. A number of studies have also found that ISG15 is capable of antagonizing replication of some viruses in tissue culture. However, recent findings have demonstrated that ISG15 can protect mice from Chikungunya virus infection without affecting the virus burden. In order to better understand the function of ISG15 in vivo, we characterized the pathogenesis of influenza A virus and Sendai virus in ISG15 ؊/؊ mice. We found that ISG15 protects mice from virus induced lethality by a conjugation-dependent mechanism in both of these models. However, surprisingly, we found that ISG15 had minimal effect on virus replication and did not have an obvious role in the modulation of the acute immune response to infection. Instead, we observed an increase in the number of diseased small airways in mice lacking ISG15. This ability of ISG15 to protect mice in a conjugationdependent, but nonantiviral, manner from respiratory virus infection represents a previously undescribed role for ISG15 and demonstrates the importance of further characterization of ISG15 in vivo. IMPORTANCE It has previously been demonstrated that ISG15؊/؊ mice are more susceptible to a number of viral infections. Since ISG15 is one of the most strongly induced genes after type I interferon stimulation, analysis of ISG15 function has largely focused on its role as an antiviral molecule during acute infection. Although a number of studies have shown that ISG15 does have a small effect on virus replication in tissue culture, few studies have confirmed this mechanism of protection in vivo. In these studies we have found that while ISG15 ؊/؊ mice are more susceptible to influenza A virus and Sendai virus infections, ISGylation does not appear to mediate this protection through the direct inhibition of virus replication or the modulation of the acute immune response. Thus, in addition to showing a novel mode of ISG15 mediated protection from virus infection, this study demonstrates the importance of studying the role of ISG15 in vivo. During acute infection, the survival of an organism is dependent on both its ability to inhibit pathogen replication, thus reducing pathogen burden, and its ability to tolerate the ensuing tissue damage incurred both from the pathogen itself, as well as from the immune response mounted against the pathogen (1, 2). Limiting pathogen replication and eventual pathogen clearance is dependent on both the innate and the adaptive immune responses. Of the many genes induced after viral infection, type I interferons ...

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“…This notion has been challenged over the past years by the (re)discovery of disease tolerance 5,6 . This evolutionarily conserved host defense strategy, which was first described in plants 7,8 , is fully operational in flies 9,10 and mammals, including rodents 11,12 and humans 13 , where it preserves host homeostasis in response to viral 14,15 , bacterial [15][16][17][18] , fungal 19 and protozoan 11,13,20,21 infections. In contrast to resistance to infection, disease tolerance does not exert a direct negative effect on these pathogens 6 .…”

Section: Introductionmentioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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Cellular Inhibitor of Apoptosis Protein cIAP2 Protects against Pulmonary Tissue Necrosis during Influenza Virus Infection to Promote Host Survival

Cited by 147 publications

References 55 publications

Tissue damage control in disease tolerance

Tissue damage control in disease tolerance

Novel Mode of ISG15-Mediated Protection against Influenza A Virus and Sendai Virus in Mice

Disease tolerance and immunity in host protection against infection

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