Macrophagic control of the response to uropathogenic E. coli infection by regulation of iron retention in an IL‐6‐dependent manner

نویسندگان

  • Nana Owusu‐Boaitey
  • Kyle A. Bauckman
  • Tingxuan Zhang
  • Indira U. Mysorekar
چکیده

INTRODUCTION Uropathogenic Escherichia coli (UPEC), the causative agent of over 85% of urinary tract infections (UTIs), elaborate a number of siderophores to chelate iron from the host. On the other hand, the host immune imperative is to limit the availability of iron to the bacteria. Little is known regarding the mechanisms underlying this host-iron-UPEC interaction. Our objective was to determine whether macrophages, in response to UPEC infection, retain extracellular siderophore-bound and free iron, thus limiting the ability of UPEC to access iron. METHODS Quantitative PCR, immunoblotting analysis, and gene expression analysis of wild type and IL-6-deficient macrophages was performed. RESULTS We found that (1) macrophages upon UPEC infection increased expression of lipocalin 2, a siderophore-binding molecule, of Dmt1, a molecule that facilitates macrophage uptake of free iron, and of the intracellular iron cargo molecule ferritin, and decreased expression of the iron exporter ferroportin; (2) bladder macrophages regulate expression of genes involved in iron retention upon UPEC infection; (3) IL-6, a cytokine known to play an important role in regulating host iron homeostasis as well as host defense to UPEC, regulates this process, in part by promoting production of lipocalin 2; and finally, (4) inhibition of IL-6 signaling genetically and by neutralizing antibodies against the IL-6 receptor, promoted intra-macrophagic UPEC growth in the presence of excess iron. CONCLUSIONS Together, our study suggests that macrophages retain siderophore-bound and free iron in response to UPEC and IL-6 signaling is necessary for macrophages to limit the growth of UPEC in the presence of excess iron. IL-6 signaling and iron regulation is one mechanism by which macrophages may mediate UPEC clearance.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Investigation of Biofilm ability by Microtiter Plate Method in uropathogenic Escherichia coli isolated from patients with urinary tract infection with urinary stones.

Abstract: Background and Aim: Urinary tract infections are one of the most commonly reported nosocomial infections caused by colonization of E. coli in the mucosal epithelium and in the formation of microbial biofilms, which damage the host tissue. The aim of this study was to determine the amount of biofilm formation of uropathogenic E. coli based on urinary tract stones of people with urin...

متن کامل

Characterization and zoonotic potential of uropathogenic Escherichia coli isolated from dogs.

The aim of this study was to investigate the characteristics of canine uropathogenic Escherichia coli (UPEC) and the interaction between canine UPEC and human bladder epithelial cells. Ten E. coli isolates collected from dogs with cystitis were analyzed for antimicrobial resistance patterns, the presence of virulence factors, and biofilm formation. The ability of these isolates to induce cytoto...

متن کامل

The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection.

Uropathogenic Escherichia coli is the causative agent for >80% of uncomplicated urinary tract infections (UTIs). Uropathogenic E. coli strains express a number of virulence and fitness factors that allow successful colonization of the mammalian bladder. To combat this, the host has distinct mechanisms to prevent adherence to the bladder wall and to detect and kill uropathogenic E. coli in the e...

متن کامل

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

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 pr...

متن کامل

Antibiotic Resistance Patterns in Enteric and Uropathogenic Strains of Escherichia Coli in Children

Abstract Background and Objective: Escherichia coli is the most common cause of urinary tract infections in children and the leading cause of intra-abdominal infections (peritonitis and abscess) followed intestinal injuries. Urinary tract infection, including cystitis and pyelonephritis, is a common childhood infection. E. coli causes more than 90 percent of the community acquired and 50% of ho...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2016