title: Malaria exacerbates experimental mycobacterial infection in vitro and in vivo.
abstract: Tuberculosis (Mtb) and malaria are among the most important infectious causes of morbidity and mortality worldwide, causing an estimated 1.5 million and 1 million deaths every year, respectively. Here we demonstrate a biological interaction between malaria and mycobacteria in vitro and in vivo. Murine macrophages co-incubated with Plasmodium falciparum parasitized erythrocytes demonstrated impaired control of intracellular Mtb replication, and reduced production of reactive nitrogen species in response to mycobacteria. Infection of C57BL/6 mice with Plasmodium species exacerbated the course of acute mycobacterial infection (57% increase in peak splenic CFU, p = 0.043 for difference over time course of infection), induced disruption of the structural integrity of established granulomas, and caused reactivation of latent mycobacterial infection (2.6-fold increase in peak splenic CFU, p = 0.016 for difference over time course of reactivation). Malaria pigment deposition within the granulomas of co-infected mice suggested that the influx of dysfunctional hemozoin-laden monocytes into the locus of mycobacterial control may contribute to impaired containment of mycobacteria. Collectively, these results point to malaria-induced dysregulation of innate and adaptive anti-mycobacterial defences, and suggest that the interaction of these globally important pathogens may potentiate Mtb infection and transmission.
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hawkes
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Maryanne
authors.initials: M
authors.lastname: Crockett
authors.forename: Angelina
authors.initials: A
authors.lastname: Diassiti
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002478:Cells, Cultured; D006099:Granuloma / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D016778:Malaria, Falciparum / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D026361:Reactive Nitrogen Species / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000150:complications*
chemical_list: D026361:Reactive Nitrogen Species