696 CNS Immunopathology in response to glycated ß-amyloid peptide in the rat brain cortex
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Amyloid (mycology)
▪ Abstract Immune responses can cause severe disease, despite the role immunity plays in defending against parasitism. Indeed, immunopathology is a remarkably common cause of disease and has strong impacts upon both host and parasite fitness. Why has immune-mediated disease not been eliminated by natural selection? What constraints might immunopathology impose upon the evolution of resistance? In this review, we explore two major mechanistic causes of immunopathology in mammals and consider how such disease may have influenced immune system design. We then propose hypotheses that could explain the failure of natural selection to eliminate immunopathology. Finally, we suggest how the evolution of strategies for parasite virulence and host resistance may be shaped by this “double-edged sword” of immunity. Future work may reveal whether immunopathology constrains the evolution of resistance in all host taxa.
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Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show that the cytokine IL-27 plays a crucial role in protection from exaggerated inflammation during influenza virus infection. Using Il-27ra−/− mice, IL-27 was found to limit immunopathology, neutrophil accumulation, and dampened TH1 or TH17 responses via IL-10–dependent and -independent pathways. Accordingly, the absence of IL-27 signals resulted in a more severe disease course and in diminished survival without impacting viral loads. Consistent with the delayed expression of endogenous Il-27p28 during influenza, systemic treatment with recombinant IL-27 starting at the peak of virus load resulted in a major amelioration of lung pathology, strongly reduced leukocyte infiltration and improved survival without affecting viral clearance. In contrast, early application of IL-27 impaired virus clearance and worsened disease. These findings demonstrate the importance of IL-27 for the physiological control of immunopathology and the potential value of well-timed IL-27 application to treat life-threatening inflammation during lung infection.
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"CD4 and the Immunopathology of AIDS." American Journal of Respiratory Cell and Molecular Biology, 1(5), pp. 349–350
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By definition, parasites harm their hosts, but in many infections much of the pathology is driven by the host immune response rather than through direct damage inflicted by parasites. While these immunopathological effects are often well studied and understood mechanistically in individual disease interactions, there remains relatively little understanding of their broader impact on the evolution of parasites and their hosts. Here, we theoretically investigate the implications of immunopathology, broadly defined as additional mortality associated with the host's immune response, on parasite evolution. In particular, we examine how immunopathology acting on different epidemiological traits (namely transmission, virulence and recovery) affects the evolution of disease severity. When immunopathology is costly to parasites, such that it reduces their fitness, for example by decreasing transmission, there is always selection for increased disease severity. However, we highlight a number of host–parasite interactions where the parasite may benefit from immunopathology, and highlight scenarios that may lead to the evolution of slower growing parasites and potentially reduced disease severity. Importantly, we find that conclusions on disease severity are highly dependent on how severity is measured. Finally, we discuss the effect of treatments used to combat disease symptoms caused by immunopathology.
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Mauthner cell
Biological neural network
Cell type
Nerve net
Neocortex
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Bursting
Cortical neurons
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Immunostaining
Pathogenesis
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