Journal article

Publication year: 2011

Journal: PLoS ONE

Volume number: 6

Issue number: 12

ISSN: 1932-6203

Open access status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0028452

Publisher: Public Library of Science

Abstract: 
Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-alpha cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key proinflammatory cytokines in PM (IL-1 alpha, IL-1 beta, IL-6 downregulated) and TM (IL-1 beta, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NF kappa B activation shown by the absence of degradation of I kappa B alpha and lack of pro-inflammatory cytokine secretion (IL-6, TNF-alpha). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells.

Harvard Citation style: Bhushan, S., Hossain, H., Lu, Y., Geisler, A., Tchatalbachev, S., Mikulski, Z., et al. (2011) Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege, PLoS ONE, 6(12), Article e28452. https://doi.org/10.1371/journal.pone.0028452

APA Citation style: Bhushan, S., Hossain, H., Lu, Y., Geisler, A., Tchatalbachev, S., Mikulski, Z., Schuler, G., Klug, J., Pilatz, A., Wagenlehner, F., Chakraborty, T., & Meinhardt, A. (2011). Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege. PLoS ONE. 6(12), Article e28452. https://doi.org/10.1371/journal.pone.0028452