Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific.
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.
Page
Kathleen R
KR
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. kpage2@jhmi.edu
Jedlicka
Anne E
AE
Fakheri
Benjamin
B
Noland
Gregory S
GS
Kesavan
Anup K
AK
Scott
Alan L
AL
Kumar
Nirbhay
N
Manabe
Yukari C
YC
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
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma