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Infection and Immunity, September 2008, p. 3924-3931, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00372-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity ^,

Emma T. Cadman,^1, Asmahan Y. Abdallah,¹ Cécile Voisine,¹ Anne-Marit Sponaas,¹ Patrick Corran,² Tracey Lamb,¹ Douglas Brown,^1,3 Francis Ndungu,¹ and Jean Langhorne^1*

Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom,¹ National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom,² Division of Molecular Immunology, National Institute for Medical Research, The Ridegway, London NW7 1AA, United Kingdom³

Received 24 March 2008/ Returned for modification 3 May 2008/ Accepted 5 June 2008

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.

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* Corresponding author. Mailing address: Division of Parasitology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom. Phone: 44 208 816 2558. Fax: 44 208 816 2638. E-mail: jlangho{at}nimr.mrc.ac.uk

Published ahead of print on 16 June 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Present address: Royal Veterinary College, Department of Veterinary Basic Sciences, Royal College Street, London NW1 0TU2, United Kingdom.

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Infection and Immunity, September 2008, p. 3924-3931, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00372-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.