Malaria exacerbates experimental mycobacterial infection in vitro and in vivo.
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.
Hawkes
Michael
M
Institute of Medical Sciences, University of Toronto, Toronto, Canada.
Li
Xiaoming
X
Crockett
Maryanne
M
Diassiti
Angelina
A
Liles
W Conrad
WC
Liu
Jun
J
Kain
Kevin C
KC
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*
D026361:Reactive Nitrogen Species