Perforin and Human Diseases

Naneh, Omar; Avčin, Tadej; Zavec, Apolonija Bedina

doi:10.1007/978-94-017-8881-6_11

Cited by 25 publications

(18 citation statements)

References 106 publications

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“…A control group of Prf −/− mice was infected with VSV alone. Perforin is the primary cytotoxic effector protein in CD8 + T cells . We found that Prf −/− mice infected with chronic LCMV and then superinfected with VSV exhibit a much more impaired B‐cell response than do Prf −/− mice infected with VSV alone (Fig.…”

Section: Resultsmentioning

confidence: 75%

Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

et al. 2015

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Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8+ T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respond to vaccination, a finding that has not been previously explained. Recently, we reported that CD169+ macrophages enforce viral replication, which is essential for guaranteeing antigen synthesis and efficient adaptive immune responses. In the present study, we used a chronic lymphocytic choriomeningitis virus infection mouse model to determine whether this mechanism is affected by chronic viral infection, which may impair the activation of adaptive immunity. We found that enforced viral replication of a superinfecting virus is completely blunted in chronically infected mice. This absence of enforced viral replication in CD169+ macrophages is not explained by CD8+ T‐cell‐mediated immunopathology but rather by prolonged IFN‐I responses. Consequently, the absence of viral replication impairs both antigen production and the adaptive immune response against the superinfecting virus. These findings indicate that chronic infection leads to sustained IFN‐I action, which is responsible for the absence of an antiviral immune response against a secondary viral infection.

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Section: Resultsmentioning

confidence: 75%

Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

et al. 2015

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“…However, the related pore-forming proteins, Perforin-1 and complement C9, are well studied and understood. Recessive mutations in PFN1 (encoding Perforin-1) are associated with poor control of viral infections and lead to the immune disorder familial hemophagocytic lymphohistiocytosis (FHL) (26). Importantly, and relevant to these variants in MPEG1, heterozygous changes in Prf1 in mice and PRF1 in humans are associated with impaired NK function and contribute to the development of hemophagocytic lymphohistiocytosis (HLH) (27,28).…”

Section: Discussionmentioning

confidence: 99%

MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections

McCormack¹,

Szymanski²,

Hsu³

et al. 2017

JCI Insight

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“…58 Indeed, mutations within PRF1 gene and defects in its expression can cause an abnormal function of the immune system. 59 …”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events

et al. 2017

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Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

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Perforin and Human Diseases

Cited by 25 publications

References 106 publications

Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events

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