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Infection and Immunity, October 2005, p. 6390-6398, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6390-6398.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Massive Destruction of Malaria-Parasitized Red Blood Cells despite Spleen Closure

Jürgen Krücken,1 Liv I. Mehnert,1 Mohamed A. Dkhil,2 Manal El-Khadragy,1 W. Peter M. Benten,1 Horst Mossmann,3 and Frank Wunderlich1*

Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich Heine University, 40225 Düsseldorf,1 Max Planck Institute of Immunobiology, 79108 Freiburg, Germany,3 Zoology Department, Helwan University, Ein Helwan, Cairo, Egypt2

Received 17 December 2004/ Returned for modification 30 January 2005/ Accepted 23 May 2005

It is currently accepted that malaria-parasitized red blood cells (pRBC) are eliminated, like senescent erythrocytes, phagocytically by macrophages in the red pulp of the spleen. Here, however, we show that self-healing Plasmodium chabaudi malaria activates spleen closure in C57BL/6 mice. Confocal laser scanning microscopy revealed that spleen closing was manifested by elimination of entry into the red pulp of 3-µm polystyrol particles, pRBC, and nonparasitized red blood cells but not of bovine serum albumin. This spleen closure did not reflect a reduction in the number of phagocytic cells, as shown by flow cytometry, whereas marginal zone macrophages (MZM) were lost and red pulp macrophages entered the white pulp. Splenic trapping of pBRC was strongly reduced in the absence of MZM and marginal metallophilic macrophages (MMM), as it is in noninfected mice with a disrupted lymphotoxin ß receptor (LTßR–/–), and it was still significantly reduced when the number of MZM and MMM was diminished, as in tumor necrosis factor alpha-deficient (TNF-{alpha}–/–) mice. Moreover, mice deficient in TNF-{alpha}, tumor necrosis factor receptor I (TNFRI–/–), and LTßR exhibited progressive impairment in malaria-induced spleen closing. Treatment of C57BL/6 mice with TNF-{alpha} induced loss of MZM and spleen closing by about 20%. Our data indicate that TNF/TNFRI signaling is involved in regulating malaria-induced spleen closure, which is maximal during crisis, when parasitemia declines more than 100-fold. Consequently, the vast majority of pRBC cannot be destroyed by the spleen during crisis, suggesting that the known sophisticated sequestration system of Plasmodium parasites did not evolve to avoid splenic clearance.

* Corresponding author. Mailing address: Heinrich Heine University of Düsseldorf, Division of Molecular Parasitology, Universitäts-str. 1, 40225 Düsseldorf, Germany. Phone: 49(0)211-8113401. Fax: 49(0)211-8114734. E-mail: frank.wunderlich{at}uni-duesseldorf.de.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2005, p. 6390-6398, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6390-6398.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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