Alterations of splenic architecture in malaria are induced independently of Toll-like receptors 2, 4, and 9 or MyD88 and may affect antibody affinity.
Splenic microarchitecture is substantially altered during acute malaria infections, which may affect the development and regulation of immune responses. Here we investigated whether engagement of host Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adaptor protein MyD88 is required for induction of the changes and whether antibody responses are modified when immunization takes place during the period of splenic disruption. The alterations in splenic microarchitecture were maximal shortly after the peak of parasitemia and were not dependent on engagement of TLR2, TLR4, or TLR9, and they were only minimally affected by the absence of the MyD88 adaptor molecule. Although germinal centers were formed in infected mice, they did not contain the usual light and dark zones. Immunization of mice with chicken gamma globulin 2 weeks prior to acute Plasmodium chabaudi infection did not affect the quantity or avidity of the immunoglobulin G antibody response to this antigen. However, immunization at the same time as the primary P. chabaudi infection resulted in a clear transient reduction in antibody avidity in the month following immunization. These data suggest that the alterations in splenic structure, particularly the germinal centers, may affect the quality of an antibody response during a malaria infection and could impact the development of immunity to malaria or to other infections or immunizations given during a malaria infection.
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Emma T
ET
Cadman
Asmahan Y
AY
Abdallah
Cécile
C
Voisine
Anne-Marit
AM
Sponaas
Patrick
P
Corran
Tracey
T
Lamb
Douglas
D
Brown
Francis
F
Ndungu
Jean
J
Langhorne
D000818:Animals; D000915:Antibody Affinity; D005260:Female; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D018512:Parasitemia; D016788:Plasmodium chabaudi / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000473:pathology*; D051193:Toll-Like Receptors / Q000172:deficiency / Q000276:immunology*
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors