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Gamma interferon levels during Chlamydia trachomatis pneumonia in mice
D M Williams1, B G Grubbs, J Schachter
1Division of Infectious Diseases, The Audie L. Murphy Veteran's Administration Hospital, San Antonio, Texas.
Abstract:
Host defense against murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) in a murine model was investigated. Gamma interferon (IFN-gamma) was produced in the lungs by both MoPn-susceptible nude athymic (nu/nu) and MoPn-resistant heterozygous (nu/+) mice. In vivo depletion of IFN-gamma in nu/nu mice led to exacerbation of infection. Fluorescence-activated cell sorter analysis disclosed induction of GL3 antibody-positive cells (putatively gamma/delta+ T cells) in nu/nu mouse lung during infection with MoPn. Treatment of nu/nu mice in vivo with antibody to NK cells (anti-asialo GM1 antibody) or to gamma/delta cells (UC7-13D5) did not significantly decrease IFN-gamma production in the lung. However, treatment of severe combined immunodeficiency mice (which lack gamma/delta cells) with antibody to NK cells significantly reduced lung IFN-gamma levels.
Insights
Host defense against Chlamydia trachomatis involves gamma interferon (IFN-gamma). Depleting IFN-gamma worsened infections in mice, highlighting its crucial role in controlling Chlamydia trachomatis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Host defense mechanisms against Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) were examined in a murine model.
- Gamma interferon (IFN-gamma) production in the lungs was observed in both susceptible (nude athymic, nu/nu) and resistant (heterozygous, nu/+) mice during MoPn infection.
Purpose of the Study:
- To investigate the role of gamma interferon (IFN-gamma) in host defense against Chlamydia trachomatis (MoPn) infection.
- To identify the immune cells involved in IFN-gamma production during MoPn infection.
Main Methods:
- In vivo depletion of IFN-gamma in MoPn-infected nude athymic (nu/nu) mice.
- Fluorescence-activated cell sorter (FACS) analysis to identify immune cell populations (GL3 antibody-positive cells, putatively gamma/delta+ T cells).
- In vivo treatment of nu/nu mice with antibodies against NK cells (anti-asialo GM1) or gamma/delta cells (UC7-13D5).
- Treatment of severe combined immunodeficiency (SCID) mice (lacking gamma/delta cells) with anti-NK cell antibody.
Main Results:
- Depletion of IFN-gamma in nu/nu mice led to exacerbated Chlamydia trachomatis infection.
- GL3 antibody-positive cells (putative gamma/delta+ T cells) were induced in the lungs of nu/nu mice during MoPn infection.
- Antibody-mediated depletion of NK cells or gamma/delta cells in nu/nu mice did not significantly reduce lung IFN-gamma levels.
- In SCID mice, NK cell depletion significantly reduced lung IFN-gamma levels.
Conclusions:
- Gamma interferon (IFN-gamma) plays a critical role in controlling Chlamydia trachomatis (MoPn) infection in mice.
- NK cells may contribute to IFN-gamma production in the lungs, particularly in the absence of gamma/delta T cells.