The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1.
ABSTRACT Virus-induced interlukin-1beta (IL-1beta) and IL-18 production in macrophages are mediated via caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome resulting in caspase-1 activation. Here, we demonstrated that Nlrp3(-/-) and Casp1(-/-) mice were more susceptible than wild-type mice after infection with a pathogenic influenza A virus. This enhanced morbidity correlated with decreased neutrophil and monocyte recruitment and reduced cytokine and chemokine production. Despite the effect on innate immunity, cryopyrin-deficiency was not associated with any obvious defect in virus control or on the later emergence of the adaptive response. Early epithelial necrosis was, however, more severe in the infected mutants, with extensive collagen deposition leading to later respiratory compromise. These findings reveal a function of the cryopyrin inflammasome in healing responses. Thus, cryopyrin and caspase-1 are central to both innate immunity and to moderating lung pathology in influenza pneumonia.
Article: Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection.[show abstract] [hide abstract]
ABSTRACT: Interleukin-1alpha (IL-1alpha) and IL-1beta are proinflammatory cytokines, which induce a plethora of genes and activities by binding to the type 1 IL-1 receptor (IL-1R1). We have investigated the role of IL-1 during pulmonary antiviral immune responses in IL-1R1(-/-) mice infected with influenza virus. IL-1R1(-/-) mice showed markedly reduced inflammatory pathology in the lung, primarily due to impaired neutrophil recruitment. Activation of CD4(+) T cells in secondary lymphoid organs and subsequent migration to the lung were impaired in the absence of IL-1R1. In contrast, activation of virus-specific cytotoxic T lymphocytes and killing of virus-infected cells in the lung were intact. Influenza virus-specific immunoglobulin G (IgG) and IgA antibody responses were intact, while the IgM response was markedly reduced in both serum and mucosal sites in IL-1R1(-/-) mice. We found significantly increased mortality in the absence of IL-1R1; however, lung viral titers were only moderately increased. Our results demonstrate that IL-1alpha/beta mediate acute pulmonary inflammatory pathology while enhancing survival during influenza virus infection. IL-1alpha/beta appear not to influence killing of virus-infected cells but to enhance IgM antibody responses and recruitment of CD4(+) T cells to the site of infection.Journal of Virology 06/2005; 79(10):6441-8. · 5.40 Impact Factor
Article: [Botulinum toxin A in dermatology].[show abstract] [hide abstract]
ABSTRACT: Based on its unique botulinum toxin is referred to as the most poisonous poison. Its specific inhibition of the acetyl-cholin-dependent neuromuscular transmission is used by ophthalmologists and neurologists for the relaxation of spastic or dystonic muscles, preferably in muscle groups in the head and neck area. Analogously, it is being used by dermatologists to remove facial wrinkles by paralyzing mimic muscles which account for mechanically induced wrinkling. Apart from this purely cosmetic use, botulinum toxin has gained recent attention in dermatology as a potent treatment modality for circumscribed hyperhidrosis.Der Hautarzt 02/1998; 49(2):87-90. · 0.58 Impact Factor