Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali.
BACKGROUND
Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood.


RESULTS
Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection.


CONCLUSIONS
These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses.
McCall
Matthew B B
MB
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hopman
Joost
J
Daou
Modibo
M
Maiga
Boubacar
B
Dara
Victor
V
Ploemen
Ivo
I
Nganou-Makamdop
Krystelle
K
Niangaly
Amadou
A
Tolo
Youssouf
Y
Arama
Charles
C
Bousema
J Teun
JT
van der Meer
Jos W
JW
van der Ven
André J A M
AJ
Troye-Blomberg
Marita
M
Dolo
Amagana
A
Doumbo
Ogobara K
OK
Sauerwein
Robert W
RW
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D004198:Disease Susceptibility / Q000208:ethnology* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000208:ethnology* / Q000276:immunology*; D008297:Male; D008302:Mali; D018512:Parasitemia / Q000208:ethnology* / Q000276:immunology; D044382:Population Groups; D055815:Young Adult
D007371:Interferon-gamma