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Chlamydia pneumoniae enhances Interleukin 8 (IL-8) production with reduced azithromycin sensitivity under hypoxia

Junji Matsuo¹, Kohei Sakai¹, Torahiko Okubo¹

¹Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica

|February 13, 2019

Abstract:

Obligate intracellular bacterium Chlamydia pneumoniae causes respiratory tract infections such as community-acquired pneumonia. During infection, C. pneumoniae induces inflammatory responses in host cells and the oxygen concentration at the infection sites subsequently decreases. Because hypoxic conditions influence further inflammatory responses and reduced antibacterial effects, this may exacerbate the C. pneumoniae infection. Here, we show inflammatory responses and drug sensitivity in C. pneumoniae-infected cells under hypoxic conditions. First, we confirmed the enhanced growth of C. pneumoniae under hypoxia, which indicates that the hypoxic condition we used could adequately reproduce past reports. We then demonstrated a significant increase in production of the pro-inflammatory cytokine Interleukin 8 (IL-8) in C. pneumoniae-infected cells under hypoxic conditions. Furthermore, hypoxia decreased the antibacterial effects of azithromycin against C. pneumoniae compared with normoxic conditions. Together, our data suggest that inflammatory responses and drug sensitivity may have been underestimated in C. pneumoniae infection in previous studies. Thus, to accurately understand the Chlamydia infection, it may be necessary to perform in vitro experiments under hypoxic conditions.

Insights

Hypoxia, or low oxygen, exacerbates Chlamydia pneumoniae infections by increasing inflammation and reducing antibiotic effectiveness. These findings highlight the need for in vitro studies under hypoxic conditions to better understand Chlamydia infections.

Area of Science:

Microbiology
Immunology
Infectious Diseases

Background:

Chlamydia pneumoniae causes respiratory infections, and inflammation during infection lowers oxygen levels (hypoxia).
Hypoxic conditions can influence inflammatory responses and antibiotic efficacy, potentially worsening C. pneumoniae infections.

Purpose of the Study:

To investigate the impact of hypoxic conditions on inflammatory responses and drug sensitivity in C. pneumoniae-infected cells.

Main Methods:

Cultured cells infected with C. pneumoniae were exposed to hypoxic conditions.
Growth of C. pneumoniae, production of Interleukin 8 (IL-8), and azithromycin efficacy were assessed under normoxic and hypoxic conditions.

Main Results:

Hypoxia significantly enhanced C. pneumoniae growth.
Pro-inflammatory cytokine IL-8 production was significantly increased in C. pneumoniae-infected cells under hypoxia.
Azithromycin's antibacterial effect against C. pneumoniae was reduced under hypoxic conditions compared to normoxic conditions.

Conclusions:

Hypoxic conditions exacerbate C. pneumoniae infections by increasing inflammation and reducing antibiotic effectiveness.
Previous studies may have underestimated the role of inflammation and drug sensitivity in C. pneumoniae infections due to a lack of hypoxic experimental conditions.
In vitro studies of Chlamydia infections should incorporate hypoxic conditions for more accurate results.

Read full analysis

Keywords:

Chlamydia pneumoniae IL-8 azithromycin hypoxic conditions

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