Journalartikel

Jahr der Veröffentlichung: 2012

Zeitschrift: PLoS ONE

Bandnummer: 7

Heftnummer: 5

ISSN: 1932-6203

Open Access Status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0037349

Verlag: Public Library of Science

Abstract: 
The peroxisomal proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPAR gamma. The relevance of PPAR gamma in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPAR gamma. This prompted us to investigate whether PPAR gamma in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPAR gamma (LysMCrexPPAR gamma(flox/flox)). Loss of PPAR gamma in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFN gamma TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPAR gamma enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6C(hi) monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPAR gamma was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPAR gamma and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPAR gamma activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection.

Harvard-Zitierstil: Abdullah, Z., Geiger, S., Nino-Castro, A., Boettcher, J., Muraliv, E., Gaidt, M., et al. (2012) Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection, PLoS ONE, 7(5), Article e37349. https://doi.org/10.1371/journal.pone.0037349

APA-Zitierstil: Abdullah, Z., Geiger, S., Nino-Castro, A., Boettcher, J., Muraliv, E., Gaidt, M., Schildberg, F., Riethausen, K., Flossdorf, J., Krebs, W., Chakraborty, T., Kurts, C., Schultze, J., Knolle, P., & Klotz, L. (2012). Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection. PLoS ONE. 7(5), Article e37349. https://doi.org/10.1371/journal.pone.0037349