Abstract
The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.
Highlights
Intracellular pathogens exploit the host machinery to promote and establish infection
We assessed the role of epithelial keratins Keratin 8 (K8) and Keratin 18 (K18), during L. monocytogenes infection. We found that both K8 and K18 are required for successful InlB/cMet-mediated internalization of L. monocytogenes and hepatocyte growth factor (HGF)-induced signaling
HeLa and Caco-2 cells were depleted for K8 and/or K18 through an siRNA approach and intracellular L. monocytogenes numbers were evaluated by gentamicin protection assays (Almeida et al, 2015)
Summary
Intracellular pathogens exploit the host machinery to promote and establish infection. The host cytoskeleton is one of the preferential targets of pathogens and plays essential roles in cellular infection (Carabeo, 2011; Haglund and Welch, 2011; de Souza Santos and Orth, 2015). The role of host actin cytoskeleton in bacterial pathogenesis is by far the most documented (Colonne et al, 2016). Actin filaments and their polymerization machinery are hijacked by several human. The role of intermediate filaments (IFs), in particular keratins, during bacterial infection is poorly characterized. IFs are part of the host cytoskeleton and include a large group of proteins that share structural features and form apolar 10 nM wide fibrous filaments (Goldman et al, 2012). Keratins are increasingly regarded as stress proteins protecting cells and tissues from stress and injury (Toivola et al, 2010)
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