title: Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific.
abstract: Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.
authors.affiliation: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. kpage2@jhmi.edu
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Page
authors.forename: Anne E
authors.initials: AE
authors.lastname: Jedlicka
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fakheri
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Noland
authors.forename: Anup K
authors.initials: AK
authors.lastname: Kesavan
authors.forename: Alan L
authors.initials: AL
authors.lastname: Scott
authors.forename: Nirbhay
authors.initials: N
authors.lastname: Kumar
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D010967:Plasmodium yoelii; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma