The Outcome of Phagocytic Cell Division with Infectious Cargo Depends on Single Phagosome Formation

Yong Luo,Lingchuan Xia,Mauricio Alvarez,Arturo Casadevall,Robin Charles May

doi:10.1371/journal.pone.0003219

Abstract

Given that macrophages can proliferate and that certain microbes survive inside phagocytic cells, the question arises as to the post-mitotic distribution of microbial cargo. Using macrophage-like cells we evaluated the post-mitotic distribution of intracellular Cryptococcus yeasts and polystyrene beads by comparing experimental data to a stochastic model. For beads, the post-mitotic distribution was that expected from chance alone. However, for yeast cells the post-mitotic distribution was unequal, implying preferential sorting to one daughter cell. This mechanism for unequal distribution was phagosomal fusion, which effectively reduced the intracellular particle number. Hence, post-mitotic intracellular particle distribution is stochastic, unless microbial and/or host factors promote unequal distribution into daughter cells. In our system unequal cargo distribution appeared to benefit the microbe by promoting host cell exocytosis. Post-mitotic infectious cargo distribution is a new parameter to consider in the study of intracellular pathogens since it could potentially define the outcome of phagocytic-microbial interactions.

Highlights

Until relatively recently it was commonly believed that macrophages were in a post-mitotic state [1,2,3]
To analyze the outcome of intracellular yeast distribution after phagocytic cell division we considered that the default outcome was stochastic, with the distribution of ingested particles or microbes after cell division reflecting chance alone
Outcome II can be Theoretical distribution index (DIT) for various numbers of intracellular particles calculated from Equation (4), with the aid of a computer program, assuming that the intracellular particles were stochastically distributed into two daughter cells during cell division

Summary

Introduction

Until relatively recently it was commonly believed that macrophages were in a post-mitotic state [1,2,3] In this scenario, dead and damaged macrophages in tissue are replenished by an influx of blood monocytes that differentiate into tissue macrophages [4,5]. Our group has shown that opsonic phagocytosis can stimulate cell cycle progression [19], through an ERK signaling mechanism (data presented at Experimental Biology 2008 meeting at San Diego, CA, Abstract #LB545). These findings suggest that local proliferation of macrophages in infected tissue could provide an alternative mechanism for the replenishment of tissue macrophages upon damage by infection

Methods

Results

Conclusion