Chlamydia spp. Infection
Chlamydiae are obligate intracellular bacteria whose classification and nomenclature are in flux. Current taxonomy features the family Chlamydiaeceae with two genera: Chlamydophila, which branches into 3 clusters, including C.
pneumoniae, C. pecorum, and a third group that contains C. psittaci, C. abortus, C. caviae, and C. felis; and Chlamydia, which branches into two major groups of C. suis and a branch containing C. trachomatis and C. muridarum. There is a growing trend to return to the genus name Chlamydia for all chlamydiae. Mice have been shown to be naturally infected with C. muridarum, the mouse pneumonitis (MoPn) agent. The MoPn agent has also been referred to as the "Nigg Agent” after Clara Nigg, who discovered the agent following serial intranasal passage of human throat washings during attempts to isolate influenza virus. Natural infections with C. psittaci are also suspected, but incompletely confirmed. Mice are experimentally susceptible to both C. trachomatis and C. psittaci of human origin. Both mouse and human agents are used in laboratory mice as contemporary models for respiratory and genital chlamydiosis and thus can serve as potential iatrogenic sources of infection in mouse colonies.Epizootiology and Pathogenesis
The prevalence of C. muridarum among wild and pet mice is unknown, and it is uncommon or absent in contemporary laboratory mouse populations. There are two widely studied MoPn agents, the Nigg and the Weiss strains. A closely related organism, SFPD, has been isolated from the intestine of hamsters. Chlamydia muridarum is closely related to, but genetically distinct from, C. trachomatis (bivars trachoma and lymphogranuloma venereum). The MoPn agent is generally believed to be transmitted by respiratory aerosols and/or by venereal transmission, but these routes are based upon experimental assumptions.
In fact, contact exposure rarely results in transmission, with evidence for the intestine being the primary target with orofecal transmission. Immunocompetent animals develop transient infections, and infections are typically silent in naturally infected mice. Experimental lung infections are more severe in BALB compared to B6 mice. Immunity to the MoPn agent is dependent upon functional CD4 T cells. B-cell-deficient (Igh6 null) mice recover from infection, but T-cell-deficient RAG, SCID, MHC class II (CD4) null, but not beta-2 microglobulin (CD8) null mice, develop severe disease. Intravaginal inoculation of the MoPn agent results in infection of the exocervical epithelium, with ascending infection of the uterus and oviducts. C3H/HeN mice developed infections of longer duration than BALB/c or B6 mice. Chronic infection of the male genital tract has also been documented experimentally.In addition, C. psittaci infects a wide range of mammals (and birds) and can experimentally cause respiratory and septicemic disease in mice. Documentation of natural infections of laboratory mice with C. psittaci is largely presumptive. In one case, intraperitoneal passage of mouse tissues resulted in splenomegaly, hepatomegaly, and serofibrinous peritonitis, and intranasal inoculation resulted in pneumonia following mouse passage.
In another, an agent was isolated following intranasal inoculation with lung tissue from enzootically infected mice, resulting in pulmonary disease. Speciation of the agents in these cases was presumed to be C. psittaci, based upon inaccurate methods (sulfadiazine resistance and glycogen staining). Experimental infection with C. psittaci is more severe in C3H, BALB/c, or A/J mice, compared to resistant B6 mice.
Pathology
Chlamydiae grow intracellularly, forming discernable elementary and reticulate bodies in the cytoplasm of infected cells. Naturally infected mice are subclinically infected. The pathology that has been described is related to mouse-passaged experimental inoculation.
Intranasal inoculation results in suppurative rhinitis, pulmonary perivascular and peribronchiolar lymphocyte infiltration, and nonsuppurative interstitial pneumonia with atelectasis, which can have significant neutrophilic leukocyte infiltration with passage or high dose. Pulmonary lesions are manifest grossly as pinpoint, elevated gray foci on the pleural surfaces. Organisms grow within bronchiolar epithelium, type 1 alveolar cells, and macrophages, which can possess intracytoplasmic vesicles containing inclusions. The MoPn agent readily disseminates hematoge- nously and by lymphatics to multiple organs, regardless of route of inoculation, due to its tropism for macrophages. It frequently infects peritoneal macrophages. Genitourinary infections are characterized by nonspecific acute and chronic inflammation.Diagnosis
Diagnosis can be made with impression smears, growth in cell culture, or embryonated chicken eggs. Accurate speciation can now be accomplished by DNA sequencing. Chlamydiae are Gram-negative but stain readily with Giemsa or Macchiavello staining methods.