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A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Chlamydia pneumoniae Lung Infection in Mice Induces Fatty Acid-Binding Protein 4-Dependent White Adipose Tissue
Yusuke Kurihara1, Nirwana Fitriani Walenna1,2, Kazunari Ishii1
1Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Abstract:
Fatty acid-binding protein 4 (FABP4) is a critical immune-metabolic modulator, mainly expressed in adipocytes and macrophages, secreted from adipocytes in association with lipolysis, and plays essential pathogenic roles in cardiovascular and metabolic diseases. We previously reported Chlamydia pneumoniae infecting murine 3T3-L1 adipocytes and causing lipolysis and FABP4 secretion in vitro. However, it is still unknown whether C. pneumoniae intranasal lung infection targets white adipose tissues (WATs), induces lipolysis, and causes FABP4 secretion in vivo. In this study, we demonstrate that C. pneumoniae lung infection causes robust lipolysis in WAT. Infection-induced WAT lipolysis was diminished in FABP4-/- mice or FABP4 inhibitor-pretreated wild-type mice. Infection by C. pneumoniae in wild-type but not FABP4-/- mice induces the accumulation of TNF-α- and IL-6-producing M1-like adipose tissue macrophages in WAT. Infection-induced WAT pathology is augmented by endoplasmic reticulum (ER) stress/the unfolded protein response (UPR), which is abrogated by treatment with azoramide, a modulator of the UPR. C. pneumoniae lung infection is suggested to target WAT and induce lipolysis and FABP4 secretion in vivo via ER stress/UPR. FABP4 released from infected adipocytes may be taken up by other neighboring intact adipocytes or adipose tissue macrophages. This process can further induce ER stress activation and trigger lipolysis and inflammation, followed by FABP4 secretion, leading to WAT pathology. A better understanding of the role of FABP4 in C. pneumoniae infection-induced WAT pathology will provide the basis for rational intervention measures directed at C. pneumoniae infection and metabolic syndrome, such as atherosclerosis, for which robust epidemiologic evidence exists.
Insights
Chlamydia pneumoniae lung infection triggers white adipose tissue lipolysis and fatty acid-binding protein 4 (FABP4) secretion in vivo. This process involves endoplasmic reticulum stress and contributes to metabolic disease pathology.
Area of Science:
- Immunology
- Metabolic disease
- Adipose tissue biology
Background:
- Fatty acid-binding protein 4 (FABP4) is an immune-metabolic modulator implicated in cardiovascular and metabolic diseases.
- Chlamydia pneumoniae infection of adipocytes in vitro induces lipolysis and FABP4 secretion.
- The in vivo effects of C. pneumoniae infection on white adipose tissue (WAT) lipolysis and FABP4 secretion remain unclear.
Purpose of the Study:
- To investigate whether Chlamydia pneumoniae intranasal lung infection targets white adipose tissues (WATs) in vivo, inducing lipolysis and FABP4 secretion.
- To elucidate the role of FABP4 and endoplasmic reticulum (ER) stress/unfolded protein response (UPR) in C. pneumoniae-induced WAT pathology.
- To explore the potential mechanisms linking C. pneumoniae infection, FABP4, and metabolic dysfunction.
Main Methods:
- Murine model of Chlamydia pneumoniae intranasal lung infection.
- Assessment of lipolysis, FABP4 secretion, and macrophage polarization in WAT.
- Utilized FABP4 knockout mice and FABP4 inhibitors.
- Investigated the role of ER stress/UPR using azoramide treatment.
Main Results:
- C. pneumoniae lung infection induced significant lipolysis in WAT.
- FABP4 deficiency or inhibition diminished infection-induced WAT lipolysis.
- Infection led to M1-like adipose tissue macrophage accumulation in wild-type but not FABP4-/- mice.
- ER stress/UPR augmented WAT pathology, which was abrogated by azoramide.
Conclusions:
- C. pneumoniae lung infection targets WAT, inducing lipolysis and FABP4 secretion in vivo, mediated by ER stress/UPR.
- FABP4 released from infected adipocytes may propagate ER stress, lipolysis, and inflammation in WAT.
- Understanding FABP4's role is crucial for developing interventions for C. pneumoniae infection and associated metabolic syndrome, like atherosclerosis.
