On the control of acute rodent malaria infections by innate immunity.
Does specific immunity, innate immunity or resource (red blood cell) limitation control the first peak of the blood-stage parasite in acute rodent malaria infections? Since mice deficient in specific immunity exhibit similar initial dynamics as wild-type mice it is generally viewed that the initial control of parasite is due to either limitation of resources (RBC) or innate immune responses. There are conflicting views on the roles of these two mechanisms as there is experimental evidence supporting both these hypotheses. While mathematical models based on RBC limitation are capable of describing the dynamics of primary infections, it was not clear whether a model incorporating the key features of innate immunity would be able to do the same. We examine the conditions under which a model incorporating parasite and innate immunity can describe data from acute Plasmodium chabaudi infections in mice. We find that innate immune response must decay slowly if the parasite density is to fall rather than equilibrate. Further, we show that within this framework the differences in the dynamics of two parasite strains are best ascribed to differences in susceptibility to innate immunity, rather than differences in the strains' growth rates or their propensity to elicit innate immunity. We suggest that further work is required to determine if innate immunity or resource limitation control acute malaria infections in mice.
Kochin
Beth F
BF
Department of Biology, Emory University, Atlanta, Georgia, United States of America. bkochin@emory.edu
Yates
Andrew J
AJ
de Roode
Jacobus C
JC
Antia
Rustom
R
D000818:Animals; D007113:Immunity, Innate / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control* / Q000662:veterinary; D051379:Mice; D018448:Models, Immunological; D016788:Plasmodium chabaudi / Q000276:immunology
Infect Immun. 2000 Nov;68(11):6127-32
11035715
Proc Biol Sci. 2008 Jun 22;275(1641):1449-58
18364317
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9161-6
15178766
J Infect Dis. 2002 Nov 1;186(9):1321-9
12402202
Proc Biol Sci. 2008 May 22;275(1639):1171-9
18292054
Parasitology. 1996 Jul;113 ( Pt 1):25-38
8710412
Parasitology. 2002 Mar;124(Pt 3):247-63
11922427
Am Nat. 2005 Nov;166(5):531-42
16224719
Exp Parasitol. 1997 Feb;85(2):206-13
9030670
Infect Immun. 1994 Sep;62(9):3761-5
8063391
Cell. 1995 Jul 14;82(1):1-4
7606774
Am Nat. 2006 Jul;168(1):41-53
16874614
J Immunol. 1994 May 1;152(9):4557-62
8157969
Med Microbiol Immunol. 2001 Apr;189(3):115-26
11388608
Infect Immun. 1991 Jan;59(1):51-8
1898902
Proc Biol Sci. 1994 Jun 22;256(1347):231-8
7914705
Parasitology. 2001 Apr;122(Pt 4):379-91
11315171
Nature. 1992 Jun 25;357(6380):689-92
1614515
Parasitology. 2002 Mar;124(Pt 3):225-35
11922425
Am Nat. 2008 Nov;172(5):214-38
18834302
Am J Trop Med Hyg. 2006 Jul;75(1):112-25
16837717
Proc Biol Sci. 2003 Feb 7;270(1512):289-98
12614579
J Theor Biol. 1994 May 21;168(2):141-50
8022194
Infect Immun. 1997 May;65(5):1593-8
9125535
Infect Immun. 1990 Oct;58(10):3225-32
2119342
Infect Immun. 1984 Jun;44(3):743-6
6373617
Proc Biol Sci. 2004 May 22;271(1543):1073-80
15293862
Nat Rev Immunol. 2004 Mar;4(3):169-80
15039754
Infect Immun. 2000 Aug;68(8):4399-406
10899836
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7624-8
15894623
Malar J. 2008 Apr 25;7:68
18439291
Am J Trop Med Hyg. 2006 Aug;75(2 Suppl):46-55
16931815
PLoS Comput Biol. 2008 Aug 22;4(8):e1000149
18725923
Nature. 2004 Jun 3;429(6991):555-8
15175751
Parasitology. 1999 Aug;119 ( Pt 2):127-33
10466119
Infect Immun. 1992 Mar;60(3):1193-201
1311705