Immunological Responses and Actin Dynamics in Macrophages Are Controlled by N-Cofilin but Are Independent from ADF

Friederike Jönsson,Bernhard Fleischer,Walter Witke,Gregor Kirfel,Christine B Gurniak,Yuntao Wu

doi:10.1371/journal.pone.0036034

Friederike Jönsson, Bernhard Fleischer + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0036034

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Abstract

Dynamic changes in the actin cytoskeleton are essential for immune cell function and a number of immune deficiencies have been linked to mutations, which disturb the actin cytoskeleton. In macrophages and dendritic cells, actin remodelling is critical for motility, phagocytosis and antigen presentation, however the actin binding proteins, which control antigen presentation have been poorly characterized. Here we dissect the specific roles of the family of ADF/cofilin F-actin depolymerizing factors in macrophages and in local immune responses.Macrophage migration, cell polarization and antigen presentation to T-cells require n-cofilin mediated F-actin remodelling. Using a conditional mouse model, we show that n-cofilin also controls MHC class II-dependent antigen presentation. Other cellular processes such as phagocytosis and antigen processing were found to be independent of n-cofilin. Our data identify n-cofilin as a novel regulator of antigen presentation, while ADF on the other hand is dispensable for macrophage motility and antigen presentation.

Highlights

The actin cytoskeleton controls cellular processes that are important for the efficacy of immune responses
N-cofilin is broadly expressed in most cell lineages, while mcofilin was found enriched in muscle, and ADF in tissues containing a lining epithelium [23,25]
Ncofilin levels were comparable in macrophages, dendritic cells and granulocytes (Fig 1A, upper panel)

Summary

Introduction

The actin cytoskeleton controls cellular processes that are important for the efficacy of immune responses These processes include cell motility [1], endocytosis [2], cell polarity and intracellular trafficking [3]. The Wiskott-Aldrich syndrome for example is caused by a mutation of the actin binding protein WASP [10], leading to defects in migration and chemotaxis of myeloid cells [11]. Certain pathogenic bacteria such as Listeria and Salmonella exploit the actin cytoskeleton to escape immune responses [12], and the entry of HI-virus to T-cells has been shown to depend on n-cofilin [13]

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