title: Coinfection with Blood-Stage Plasmodium Promotes Systemic Type I Interferon Production during Pneumovirus Infection but Impairs Inflammation and Viral Control in the Lung.
abstract: Acute lower respiratory tract infections (ALRTI) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hRSV) being a major cause of viral ALRTI in young children worldwide. In sub-Saharan Africa, many young children experience severe illnesses due to hRSV or Plasmodium infection. Although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. Recent data show that febrile young children infected with Plasmodium are often concurrently infected with respiratory viral pathogens but are less likely to suffer from pneumonia than are non-Plasmodium-infected children. Here, we hypothesized that blood-stage Plasmodium infection modulates pulmonary inflammatory responses to a viral pathogen but does not aid its control in the lung. To test this, we established a novel coinfection model in which mice were simultaneously infected with pneumovirus of mice (PVM) (to model hRSV) and blood-stage Plasmodium chabaudi chabaudi AS (PcAS) parasites. We found that PcAS infection was unaffected by coinfection with PVM. In contrast, PVM-associated weight loss, pulmonary cytokine responses, and immune cell recruitment to the airways were substantially reduced by coinfection with PcAS. Importantly, PcAS coinfection facilitated greater viral dissemination throughout the lung. Although Plasmodium coinfection induced low levels of systemic interleukin-10 (IL-10), this regulatory cytokine played no role in the modulation of lung inflammation or viral dissemination. Instead, we found that Plasmodium coinfection drove an early systemic beta interferon (IFN-β) response. Therefore, we propose that blood-stage Plasmodium coinfection may exacerbate viral dissemination and impair inflammation in the lung by dysregulating type I IFN-dependent responses to respiratory viruses.
authors.affiliation: Malaria Immunology Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Edwards
authors.affiliation: Laboratory for Respiratory Mucosal Immunity, School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
authors.forename: Vivian
authors.initials: V
authors.lastname: Zhang
authors.affiliation: Laboratory for Respiratory Mucosal Immunity, School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
authors.forename: Rhiannon B
authors.initials: RB
authors.lastname: Werder
authors.affiliation: Malaria Immunology Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Best
authors.affiliation: Malaria Immunology Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Ismail
authors.initials: I
authors.lastname: Sebina
authors.affiliation: Malaria Immunology Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Kylie R
authors.initials: KR
authors.lastname: James
authors.affiliation: Immunology and Infection Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Faleiro
authors.affiliation: Immunology and Infection Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Fabian
authors.initials: F
authors.lastname: de Labastida Rivera
authors.affiliation: Immunology and Infection Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Amante
authors.affiliation: Immunology and Infection Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
authors.affiliation: Laboratory for Respiratory Mucosal Immunity, School of Biomedical Sciences, The University of Queensland, Queensland, Australia Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.affiliation: Malaria Immunology Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, Australia ashraful.haque@qimrbergofer.edu.au.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
mesh_terms: D000818:Animals; D001990:Bronchiolitis, Viral / Q000276:immunology* / Q000821:virology; D060085:Coinfection; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000469:parasitology / Q000821:virology; D016899:Interferon-beta / Q000097:blood / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology*; D008288:Malaria / Q000150:complications / Q000276:immunology*; D016788:Plasmodium chabaudi; D018111:Pneumovirus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D018186:Pneumovirus Infections / Q000150:complications / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity; D019562:Viral Load; D015431:Weight Loss
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10; D016899:Interferon-beta