S. mansoni Bolsters Anti-Viral Immunity in the Murine Respiratory Tract

Abstract

The human intestinal parasite Schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. According to the current literature, the parasite induces vigorous immune responses that are controlled by Th2 helper cells at the expense of Th1 helper cells. The latter cell type is, however, indispensable for anti-viral immune responses. Remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respiratory tract, for instance against influenza A virus or against respiratory syncitial virus (RSV). We therefore re-examined the immune response to a human isolate of S. mansoni and challenged mice in the chronic phase of schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a mouse virus to model RSV infections. We found that mice with chronic schistosomiasis had significant, systemic immune responses induced by Th1, Th2, and Th17 helper cells. High serum levels of TNF-α, IFN-γ, IL-5, IL-13, IL-2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of diseased mice showed low-grade inflammation, with goblet cell hyperplasia and excessive mucus secretion, which was alleviated by treatment with an anti-TNF-α agent (Etanercept). Mice with chronic schistosomiasis were to a relative, but significant extent protected from a secondary viral respiratory challenge. The protection correlated with the onset of oviposition and TNF-α-mediated goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are involved in enhanced immune protection to respiratory viruses during chronic murine schistosomiasis. Indeed, also in a model of allergic airway inflammation mice were protected from a viral respiratory challenge with PVM.

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

“…As described above, bacterial pathogens given prior to influenza viruses can stimulate innate immunity that reduces the severity of influenza (56,58). Infection of mice with nonpathogenic bacteria or with a parasite that causes a chronic infection has also been shown to reduce the severity of influenza infections (34,(62)(63)(64)(65). While the mechanisms of protection may differ among coinfecting microbes, protection relies on detection of the initial infection by pattern recognition receptors.…”

Viral–bacterial interactions in the respiratory tract

“…Finally, interactions are not restricted locally, but can be linked to systemic or distal causes [e.g. general immunosuppression due to human immunodeficiency virus (HIV)/AIDS and susceptibility to tuberculosis (Nunn et al, 2005), or immunomodulatory effects of helminths (Scheer et al, 2014)]. …”

Signaling via pattern recognition receptors NOD2 and TLR2 contributes to immunomodulatory control of lethal pneumovirus infection

“…We and others have explored inflammatory responses to and immunomodulatory control of respiratory virus infection using the pneumonia virus of mice (PVM) model of acute pneumovirus infection (Dyer et al , 2012; Bondue et al , 2011; Walsh et al , 2014; Scheer et al , 2014; Siegle et al , 2011). PVM is closely related to RSV; however, unlike RSV, PVM undergoes robust replication in vivo , most prominently in bronchial epithelial cells of inbred strains of mice.…”