On the Control of Acute Rodent Malaria Infections by Innate Immunity

Beth F Kochin,Rustom Antia,Andrew J Yates,Jacobus C De Roode,Lisa F P Ng

doi:10.1371/journal.pone.0010444

Abstract

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.

Highlights

Understanding what controls the initial decline in pathogen density during the acute phase of infections is an important and largely unsolved problem
Because of the wealth of data available on the early dynamics of parasite and red blood cells (RBCs) in mice infected with Plasmodium chabaudi, we focus on this system
In File S1, section 2, we show how the dynamics arising from this simple model of parasite growth and clearance in the blood are indistinguishable from those obtained with a fuller description of RBC infection and dynamics

Summary

Introduction

Understanding what controls the initial decline in pathogen density during the acute phase of infections is an important and largely unsolved problem. Three mechanisms may cause this decline: (i) the specific immune responses of the host; (ii) the innate immune response of the host; and (iii) the availability of resources, such as target cells, that are required for pathogen replication. During the acute phase of primary malaria infection the parasite grows exponentially to a high density through replication in red blood cells (RBCs), and subsequently declines. Mice lacking B or T cells exhibit early parasite dynamics that are very similar to those in wild type mice [6,7,8,9]. This observation leaves us with the resource limitation and innate immunity hypotheses

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Results

Conclusion