Human immunopathogenesis of severe acute respiratory syndrome (SARS)

Abstract

Progressive immune-associated injury is a hallmark of severe acute respiratory syndrome (SARS). Viral evasion of innate immunity, hypercytokinemia and systemic immunopathology in the SARS coronavirus (SARS CoV) infected host have been suggested as possible mechanisms for the cause of severe pathology and morbidity in SARS patients. The molecular and cellular basis for how SARS CoV impacts the host immune system resulting in severe SARS, however, has not been elucidated. The variable clinical course of SARS may be the result of complex programs of host responses against the infectious agent. Therefore, the systematic analysis of innate and adaptive immune responses to SARS CoV is imperative in building as complete an immunological model as possible of host immunity and inflammatory responses during illness. Here we review recent advances in SARS immunopathogenesis research and present a summary of our findings regarding host responses in SARS patients. We contend that dysregulated type I and II interferon (IFN) responses during SARS may culminate in a failure of the switch from hyper-innate immunity to protective adaptive immune responses in the human host.

A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo

“…Since MA15-infected mice had lower mortality than v2163-infected mice, MIP-1α and RANTES may not be good indicators of disease outcome. When comparing the mouse cytokine profile to that detected in human SARS patients, the majority of human studies showed the same profile as seen in mice for IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10 and MCP-1 (Cameron et al, 2008; Chen and Subbarao, 2007; Hsueh et al, 2004; Zhu, 2004)(Table 6). In contrast, IL-1β was not elevated in mouse lungs or in human lungs, but 3 of 5 serum studies reviewed showed elevated IL-1β in human patients.…”

“… + = cytokine elevated 0 = cytokine not elevated ND = not determined a Source: Chen and Subbarao, 2007 b Sources: Hsueh et al, 2004; Cameron et al, 2008, Review of Chen and Subbarao, 2007, review of Zhu, 2004. c Separate study currently in press. …”

Ginsenoside Rg1 improves lipopolysaccharide-induced acute lung injury by inhibiting inflammatory responses and modulating infiltration of M2 macrophages

“…The increased concentration of proinflammatory cy-272 tokines (eg, TNF-α, IL-1β and IL-6) in BALF has been noted to be in 273 accordance with the severity of ALI [13,14]. Continuous elevation of 274 the cytokines mentioned above in patients suffering from ALI indicated 275 a poor outcome[32]. These proinflammatory cytokines magnify the…”

Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice

“…Viruses may differ substantially in the amount of host cell damage they cause during their replication (7,17,57,62,67). The immune response presents a powerful barrier against viruses and can target both cell-free viruses and virus-infected cells.…”