In vivo characterization of the underlying immunologic mechanisms of disease modulation in the context of Toxoplasma Gondii and influenza A Virus Co-infections

Abstract

Toxoplasma gondii (T. gondii), an obligate eukaryotic intracellular protozoan parasite, is the causative agent of toxoplasmosis. In immunocompetent individuals, T. gondii infections are usually asymptomatic; however, some patients may present with flu-like symptoms and sometimes lymphadenophathy. Contrarily, in immunocompromised patients, the infection may be life threatening. Another spectrum of the disease is congenital toxoplasmosis, which may lead to abortion, or severe fetal outcomes including mental retardation, hydrocephaly, microcephaly, chorioretinitis and impaired vision in newborn infants. Influenza A virus (IAV) is a major cause of acute respiratory tract infections in humans, which occasionally cause pandemics. Severe influenza infections are characterized by complications like pneumonia, encephalitis, and secondary bacterial pneumonia. Infection with T. gondii has been shown to modulate the outcomes of disease in the context of infection with other pathogens like Helicobacter felis, Trichinalla spiralis, and Mycobacterium avium. However, no studies investigated the disease outcome and underlying immunologic mechanisms of IAV infection in the context of acute toxoplasmosis. Therefore, the aim of this study is to characterize the effect of co-infections and the underlying immune response with these two pathogens in mice. Six-to-eight weeks old female BALB-c mice were intraperitoneally infected with tachyzoites of a type II T. gondii strain followed by the intranasal inoculation with IAV or vice versa. Mouse survival and weight change were monitored over the course of three weeks of infection. Acute toxoplasmosis was verified by western blot. Real time PCR and plaque assay (for IAV) were used for quantification of parasitic and viral loads within the lungs and peritoneal lavage, respectively, during the acute toxoplasmosis stage. In addition, quantitative real time PCR was used to quantify expression of pro and anti-inflammatory cytokines in the in the spleen and lungs of singly infected and co-infe