Worlds worst parasitic worms news.sciencemag.org/biology/2014/07/slideshow-worlds-worst-parasitic-worms Hookworms, roundworms, and other species of parasitic worms known as helminths have thrived in mammals for millions of years. Despite modern strides in sanitation, helminth infections still have a devastating impact on human health and well-being, especially in developing regions. This week, Science features two research papers that explore how parasitic infections can compromise the immune system by reawakening latent viruses and impeding antiviral defenses. The worms in this slideshow are responsible for some of the nastiest helminth infections in the world and cause a global burden of disease that outweighs better-known infections such as malaria and tuberculosis. For more, see this week’s issue of Science (Science Magazine 1 August 2014 Cover - sciencemag.org/content/345/6196.cover-expansion). References 1. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation Science 1 August 2014: Vol. 345 no. 6196 pp. 578-582 DOI: 10.1126/science.1256942 sciencemag.org/content/345/6196/578.abstract Editors Summary Parasites make it hard to fight viruses Microbial co-infections challenge the immune system—different pathogens often require different flavors of immune responses for their elimination or containment (see the Perspective by Maizels and Gause). Two teams studied what happens when parasitic worms and viruses infect mice at the same time. Reese et al. found that parasite co-infection woke up a dormant virus. Osborne et al. found that mice already infected with parasitic worms were worse at fighting off viruses. In both cases, worms skewed the immune response so that the immune cells and the molecules they secreted created an environment favorable for the worm at the expense of antiviral immunity. Science, this issue p. 573 (2) and p. 578 (1); see also p. 517 (3) Abstract The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1. 2. Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter Science 1 August 2014: Vol. 345 no. 6196 pp. 573-577 DOI: 10.1126/science.1254517 sciencemag.org/content/345/6196/573 Abstract Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi’s sarcoma–associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNγ reactivated latent murine γ-herpesvirus infection in vivo, suggesting a “two-signal” model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status. 3. How helminths go viral Science 1 August 2014: Vol. 345 no. 6196 pp. 517-518 DOI: 10.1126/science.1258443 sciencemag.org/content/345/6196/517 Research into infectious diseases is generally highly reductionist, focusing on the disease-causing agent while meticulously excluding extraneous factors, such as unrelated pathogens. But the real world is quite different, with multiple concurrent microorganisms (viruses, bacteria) and macro-organisms (parasites), each with differing dynamics and impacts on the host (1). Many of these agents are relatively neglected, especially those such as the helminth worms (see the photo). They also predominantly affect people in low-income tropical environments and influence susceptibility to a range of other infectious diseases (2). On pages 573 and 578 of this issue, Reese et al. (3) and Osborne et al. (4), respectively, provide fine detail on how helminth worms can substantially enhance and reactivate viral infection, with major health implications for tropical medicine.
Posted on: Fri, 08 Aug 2014 20:36:14 +0000