Chlamydia muridarum infection causes bronchointerstitial pneumonia in NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice Journal Article
| Authors: | St Jean, S. C.; Ricart Arbona, R. J.; Mishkin, N.; Monette, S.; Wipf, J. R. K.; Henderson, K. S.; Cheleuitte-Nieves, C.; Lipman, N. S.; Carrasco, S. E. |
| Article Title: | Chlamydia muridarum infection causes bronchointerstitial pneumonia in NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice |
| Abstract: | The murine bacterial pathogen Chlamydia muridarum (Cm) has been used to study human Chlamydia infections in various mouse models. CD4+ T-cells, natural killer cells, and interferon-gamma (IFN-γ)–mediated immunity are important to control experimentally induced Cm infections. Despite its experimental use, natural infection by Cm has not been documented in laboratory mice since the 1940s. In 2022, the authors reported the discovery of natural Cm infections in numerous academic institutional laboratory mouse colonies around the globe. To evaluate the impact of Cm infection in severely immunocompromised mice, 19 NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice were cohoused with Cm shedding, naturally infected immunocompetent mice and/or their soiled bedding for 4 weeks and subsequently euthanized. Clinical disease, characterized by lethargy, dyspnea, and weight loss, was observed in 11/19 NSG mice, and 16/18 NSG mice had neutrophilia. All mice exhibited multifocal to coalescing histiocytic and neutrophilic bronchointerstitial pneumonia (17/19) or bronchiolitis (2/19) with intraepithelial chlamydial inclusions (CIs). Immunofluorescence showed CIs were often associated with bronchiolar epithelium. CIs were frequently detected by immunohistochemistry in tracheal and bronchiolar epithelium (19/19), as well as throughout the small and large intestinal epithelium without lesions (19/19). In a subset of cases, Cm colonized the surface epithelium in the nasopharynx (16/19), nasal cavity (7/19), and middle ear canal (5/19). Endometritis and salpingitis with intraepithelial CI were identified in a single mouse. These findings demonstrate that Cm infection acquired through direct contact or soiled bedding causes significant pulmonary pathology and widespread intestinal colonization in NSG mice. © The Author(s) 2023. |
| Keywords: | immunohistochemistry; adult; controlled study; dna binding protein; gene sequence; dna-binding proteins; histopathology; nonhuman; t lymphocyte; mouse; animal; animals; mice; animal tissue; prevalence; animal experiment; animal model; immunofluorescence; mice, scid; histology; dyspnea; pneumonia; in situ hybridization; immune response; neutrophil; gamma interferon; veterinary medicine; escherichia coli; cd4+ t lymphocyte; natural killer cell; interleukin receptor common gamma subunit; innate immunity; real time polymerase chain reaction; histiocyte; staphylococcus aureus; bacterial colonization; microbiology; mice, inbred nod; matrix assisted laser desorption ionization time of flight mass spectrometry; lethargy; nonobese diabetic mouse; endoscopy; streptococcus pneumoniae; dna extraction; leukocytosis; scid mouse; interleukin 2 receptor gamma; monocytosis; nose cavity; pseudomonas aeruginosa; transmission electron microscopy; bronchiolitis; lymphocytic choriomeningitis virus; dna dependent protein kinase; citrobacter rodentium; dna-activated protein kinase; klebsiella oxytoca; klebsiella pneumoniae; lamina propria; outer membrane protein; meningoencephalitis; body weight loss; neutrophilia; endometritis; chlamydia infections; rodent diseases; staphylococcus epidermidis; tracheitis; humans; human; male; female; article; immunofluorescence assay; streptobacillus moniliformis; salpingitis; ectromelia virus; small intestine epithelium; bronchopneumonia; clostridioides difficile; mammalian orthoreovirus 3; chlamydia muridarum; bronchointerstitial pneumonia; elementary bodies; intraepithelial chlamydial inclusions (cis); major outer membrane protein; nod.cg-prkdc<sup>scid</sup>il2rg<sup>tm1wjl</sup>/szj; reticulate bodies; il2rg protein, mouse; prkdc protein, mouse; actinomyces naeslundii; bronchiole epithelium; chlamydia infection; elementary body; large intestine epithelium; reticulate body; staphylococcus hominis; rodent disease |
| Journal Title: | Veterinary Pathology |
| Volume: | 61 |
| Issue: | 1 |
| ISSN: | 0300-9858 |
| Publisher: | Sage Publications |
| Date Published: | 2024-01-01 |
| Start Page: | 145 |
| End Page: | 156 |
| Language: | English |
| DOI: | 10.1177/03009858231183907 |
| PUBMED: | 37434451 |
| PROVIDER: | scopus |
| PMCID: | PMC11323309 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Sebastian Carrasco -- Source: Scopus |
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