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Role For Inducible Nitric Oxide Synthase In Protection From Chronic Chlamydia Trachomatis Urogenital Disease In Mice And Its Regulation By Oxygen Free Radicals

K. Ramsey, I. Sigar, S. Rana, J. Gupta, S. Holland, G. Byrne
Published 2001 · Biology, Medicine

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ABSTRACT It has been previously reported that although inducible nitric oxide synthase (iNOS) gene knockout (NOS2−/−) mice resolve Chlamydia trachomatis genital infection, the production of reactive nitrogen species (RNS) via iNOS protects a significant proportion of mice from hydrosalpinx formation and infertility. We now report that higher in vivo RNS production correlates with mouse strain-related innate resistance to hydrosalpinx formation. We also show that mice with a deletion of a key component of phagocyte NADPH oxidase (p47phox−/−) resolve infection, produce greater amounts of RNS in vivo, and sustain lower rates of hydrosalpinx formation than both wild-type (WT)NOS2+/+ andNOS2−/− controls. When we induced an in vivo chemical block in iNOS activity in p47phox−/− mice usingNG-monomethyl-l-arginine (L-NMMA), a large proportion of these mice eventually succumbed to opportunistic infections, but not before they resolved their chlamydial infections. Interestingly, when compared to WT and untreated p47phox−/− controls, L-NMMA-treated p47phox−/− mice resolved their infections more rapidly. However, L-NMMA-treated p47phox−/− mice lost resistance to chronic chlamydial disease, as evidenced by an increased rate of hydrosalpinx formation that was comparable to that forNOS2−/− mice. We conclude that phagocyte oxidase-derived reactive oxygen species (ROS) regulate RNS during chlamydial urogenital infection in the mouse. We further conclude that while neither phagocyte oxidase-derived ROS nor iNOS-derived RNS are essential for resolution of infection, RNS protect from chronic chlamydial disease in this model.
This paper references
Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis
H. Caldwell (1981)
Chronic chlamydial genital infection in congenitally athymic nude mice.
R. Rank (1985)
Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide.
D. Stuehr (1985)
Activation of latent collagenase from polymorphonuclear leukocytes by oxygen radicals.
Harald Burkhardt (1986)
Mouse model for protective immunity to chlamydia, p. 236–240
G. I. Byrne (1990)
Mouse model for protective immunity to chlamydia
G I Byrne (1990)
Immune responses to Chlamydia are protective and pathogenic
R. P. Morrison (1990)
Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines
K. Ramsey (1991)
Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine.
D. Granger (1991)
Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells.
J. Mayer (1993)
Intravaginal inoculation of mice with the Chlamydia trachomatis mouse pneumonitis biovar results in infertility
L. M. de la Maza (1994)
Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis.
W. Beatty (1994)
Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection
T. W. Cotter (1995)
The p47phox mouse knock-out model of chronic granulomatous disease
S. H. Jackson (1995)
Nitric oxide and oxygen radicals: a question of balance
V. Darley-Usmar (1995)
Gene knockout mice establish a primary protective role for major histocompatibility complex class II-restricted responses in Chlamydia trachomatis genital tract infection
R. Morrison (1995)
CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract
H. Su (1995)
The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated
R. Ingalls (1995)
Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae
T. Darville (1995)
Intranasal immunization induces long-term protection in mice against a Chlamydia trachomatis genital challenge
S. Pal (1996)
Susceptibility of Chlamydia trachomatis to protegrins and defensins
B. Yasin (1996)
Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.
S. Rajagopalan (1996)
The molecular mechanism of T-cell control of Chlamydia in mice: role of nitric oxide.
J. Igietseme (1996)
Molecular mechanism of T‐cell control of Chlamydia in mice: role of nitric oxide in vivo
J. Igietseme (1996)
Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque
S. Rajagopalan (1996)
Role of oxidants in microbial pathophysiology.
R. Miller (1997)
Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways.
L. Perry (1997)
Mouse strain-dependent variation in the course and outcome of chlamydial genital tract infection is associated with differences in host response
T. Darville (1997)
Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice
T. W. Cotter (1997)
Reactivation of chlamydial genital tract infection in mice
T. W. Cotter (1997)
Effects of reactive metabolites of oxygen and nitrogen on gelatinase A activity.
M. Owens (1997)
Response of Chlamydia trachomatis serovar E to iron restriction in vitro and evidence for iron-regulated chlamydial proteins
J. Raulston (1997)
Inducible Nitric Oxide Synthase Does Not Affect Resolution of Murine Chlamydial Genital Tract Infections or Eradication of Chlamydiae in Primary Murine Cell Culture
K. Ramsey (1998)
Neither Interleukin-6 nor Inducible Nitric Oxide Synthase Is Required for Clearance of Chlamydia trachomatis from the Murine Genital Tract Epithelium
L. Perry (1998)
Vaccination against Chlamydial Genital Tract Infection after Immunization with Dendritic Cells Pulsed Ex Vivo with Nonviable Chlamydiae
H. Su (1998)
Transforming growth factor- is associated with increased pathology in -interferon gene knockout mice infected with Chlamydiae, p. 407–410
T. Darville (1998)
Transforming growth factor -  is associated with increased pathology in  - interferon gene knockout mice infected with Chlamydiae
L. R. Kishen (1998)
Nitric oxide suppresses human T lymphocyte proliferation through IFN-gamma-dependent and IFN-gamma-independent induction of apoptosis.
A. Allione (1999)
Chlamydia: Intracellular Biology, Pathogenesis, And Immunity
R. Stephens (1999)
T-Cell Responses during Trypanosoma brucei Infections in Mice Deficient in Inducible Nitric Oxide Synthase
A. Millar (1999)
Models of Immunity
R. Rank (1999)
Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase.
M. Shiloh (1999)
T-Cell Hyporesponsiveness Induced by Activated Macrophages through Nitric Oxide Production in Mice Infected withMycobacterium tuberculosis
S. Nabeshima (1999)
Models of immunity, p. 239–295
R. G. Rank (1999)
Nitric oxide suppresses human T lymphocyte proliferation through IFN- -dependent and IFN- -independent induction of apoptosis
A. Allione (1999)
Does Inhibition of Tumor Necrosis Factor Alpha Affect Chlamydial Genital Tract Infection in Mice and Guinea Pigs?
T. Darville (2000)
Amplification of IL-1β-Induced Matrix Metalloproteinase-9 Expression by Superoxide in Rat Glomerular Mesangial Cells Is Mediated by Increased Activities of NF-κB and Activating Protein-1 and Involves Activation of the Mitogen-Activated Protein Kinase Pathways1
W. Eberhardt (2000)
Superoxide Prevents Nitric Oxide-Mediated Suppression of Helper T Lymphocytes: Decreased Autoimmune Encephalomyelitis in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Knockout Mice1
R. C. van der Veen (2000)
Chlamydia trachomatis Persistence in the Female Mouse Genital Tract: Inducible Nitric Oxide Synthase and Infection Outcome
K. Ramsey (2001)
Early Local Cytokine Profiles in Strains of Mice with Different Outcomes from Chlamydial Genital Tract Infection
T. Darville (2001)

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G. Häcker (2018)
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Tom Zortel (2018)
Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine.
Taylor B Poston (2018)
Immunopathogenesis of Chlamydial Infections.
A. Murthy (2018)
Activation of neutrophils by Chlamydia trachomatis-infected epithelial cells is modulated by the chlamydial plasmid.
S. Lehr (2018)
Chlamydial Plasmid-Dependent Pathogenicity.
G. Zhong (2017)
The role of regulatory T and B cells in host responses to Chlamydia genital tract infection
J. Moore-Connors (2016)
Sensing the enemy, containing the threat: cell-autonomous immunity to Chlamydia trachomatis.
Ryan Finethy (2016)
Reverse transendothelial migration of intimal CD11c + dendritic cells: Role in intracellular pathogen removal and effect on atherosclerotic lesions
Mark Roufaiel (2016)
iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.
N. Fujii (2016)
The p47phox deficiency significantly attenuates the pathogenicity of Chlamydia muridarum in the mouse oviduct but not uterine tissues.
J. Dai (2016)
Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.
M. Wolfson (2015)
Animal models of immunity to female genital tract infections and vaccine development
C. Kaushic (2015)
Chlamydial Induction of Hydrosalpinx in 11 Strains of Mice Reveals Multiple Host Mechanisms for Preventing Upper Genital Tract Pathology
Jianlin Chen (2014)
Lack of Long-Lasting Hydrosalpinx in A/J Mice Correlates with Rapid but Transient Chlamydial Ascension and Neutrophil Recruitment in the Oviduct following Intravaginal Inoculation with Chlamydia muridarum
Hongbo Zhang (2014)
Immunity, immunopathology, and human vaccine development against sexually transmitted Chlamydia trachomatis
J. Rey-Ladino (2014)
chlamydial ascension and neutrophil recruitment in the oviduct following intravaginal 3
H. Zhang (2014)
Complement Factor C5 but Not C3 Contributes Significantly to Hydrosalpinx Development in Mice Infected with Chlamydia muridarum
Zhangsheng Yang (2014)
Characterizing the role of innate and adaptive immune responses in the pathogenesis of Chlamydia genital tract infection
Lauren C. Frazer (2013)
21 Chlamydial Diseases
R. M. Johnson (2013)
Murine Chlamydia psittaci Infection Innate Immunity and Inflammation to The p47 GTPases Iigp2 and Irgb10 Regulate
Gerald I. Byrne (2013)
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Lingli Tang (2013)
Perforin-2 Restricts Growth of Chlamydia trachomatis in Macrophages
K. A. Fields (2013)
Determinants of Upper Genital Tract Complications in a Chlamydial Urogenital Mouse Model
Enitra N Jones (2013)
Comprehensive analysis of the impact of endemic Chlamydia pecorum infection in cattle
Anil Poudel (2012)
Cervical nitric oxide release in Chlamydia trachomatis and high‐risk human papillomavirus infection
Päivi Rahkola (2011)
Chlamydiales and the innate immune response: friend or foe?
B. Rusconi (2011)
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