Parasites suppress immune response to other pathogens

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http://iai.asm.org/cgi/content/full/73/6/3531

 

Infection and Immunity, June 2005, p. 3531-3539, Vol. 73, No. 6

0019-9567/05/$08.00+0 doi:10.1128/IAI.73.6.3531-3539.2005

http://iai.asm.org/cgi/content/full/73/6/3531

 

 

 

2005, American Society for Microbiology. .

Impairment of Protective Immunity to Blood-Stage Malaria by Concurrent

Nematode Infection

Zhong Su,1,2* Mariela Segura,1,2 Kenneth Morgan,1,3 J. Concepcion

Loredo-Osti,1 and Mary M. Stevenson1,2

 

McGill Centre for the Study of Host Resistance, Research Institute of

McGill University Health Centre,1 McGill Centre for Host-Parasite

Interactions, Institute of Parasitology, McGill University, Ste Anne

de Bellevue, Quebec, Canada,2 Departments of Human Genetics and

Medicine, McGill University, Montreal3

 

Received 12 October 2004/ Returned for modification 19 November 2004/

Accepted 2 February 2005

 

 

Helminthiases, which are highly prevalent in areas where malaria is

endemic, have been shown to modulate or suppress the immune response

to unrelated antigens or pathogens. In this study, we established a

murine model of coinfection with a gastrointestinal nematode parasite,

Heligmosomoides polygyrus, and the blood-stage malaria parasite

Plasmodium chabaudi AS in order to investigate the modulation of

antimalarial immunity by concurrent nematode infection. Chronic

infection with the nematode for 2, 3, or 5 weeks before P. chabaudi AS

infection severely impaired the ability of C57BL/6 mice to control

malaria, as demonstrated by severe mortality and significantly

increased malaria peak parasitemia levels. Coinfected mice produced

significantly lower levels of gamma interferon (IFN-{gamma}) during P.

chabaudi AS infection than mice infected with malaria alone.

Concurrent nematode infection also suppressed production of type

1-associated, malaria-specific immunoglobulin G2a. Mice either

infected with the nematode alone or coinfected with the nematode and

malaria had high transforming growth factor ß1 (TGF-ß1) levels, and

concurrent nematode and malaria infections resulted in high levels of

interleukin-10 in vivo. Splenic CD11c+ dendritic cells (DC) from mice

infected with malaria alone and coinfected mice showed similarly

increased expression of CD40, CD80, and CD86, but DC from coinfected

mice were unable to induce CD4+ T-cell proliferation and optimal

IFN-{gamma} production in response to the malaria antigen in vitro.

Importantly, treatment of nematode-infected mice with an anthelmintic

drug prior to malaria infection fully restored protective antimalarial

immunity and reduced TGF-ß1 levels. These results demonstrate that

concurrent nematode infection strongly modulates multiple aspects of

immunity to blood-stage malaria and consequently impairs the

development of protective antimalarial immunity.

 

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