Mycoplasma pulmonis Infection: Murine Respiratory Mycoplasmosis

Chronic respiratory disease in rats has undergone an interesting historical evolution. Initially believed to be multifactorial, it later became apparent that M. pulmonis could be the primary pathogen in this disease.

Epizootiology and Pathogenesis

Quality control programs in laboratory animal medicine have resulted in a marked reduction in the incidence of

FIG. 2.21. Electron micrograph of bronchiolar epithelium heavily colonized with Mycoplasma pulmonis, resulting in complete loss ofcilia.

myocoplasmosis in rats. However, based on serological surveys, seropositive colonies continue to be identified, and infection in wild and pet rats is common. Transmis­sion of M. pulmonis among cage-mates and to adjacent cages occurs inefficiently by aerosols.

Mycoplasma pulmonis has an affinity for respiratory epithelium, middle ear, endometrium, and less com­monly, synovium. Invasion of the middle ear probably occurs via the Eustachian tube. This usually results in a chronic otitis media, since the Eustachian tube opens into the tympanic bulla on the dorsal aspect, affording poor drainage to the nasopharynx. Colonization of res­piratory epithelium results in ciliostasis, with resulting impaired airway clearance and accumulation of lyso­zyme-rich inflammatory exudate. Since intrapulmonary airways lack cartilage, bronchioles are subject to bronchiolar expansion and bronchiolectasis. Host cell damage may occur by a variety of means including uptake of essential cell metabolites and release of cyto­toxic substances such as H₂O₂. Both the intact organisms and the cell membranes are nonspecific B-cell mitogens, resulting in marked peribronchiolar lymphocytic infil­tration, which is a hallmark of CRD in the rat.

Pathology

Clinical signs vary, including subclinical infections, but can include minimal to florid respiratory distress, snif­fling, torticollis, infertility, and arthritis. In severely affected animals, dyspnea, ruffled hair coat, and weight loss may occur. Porphyrin-containing dark red encrusta­tions may be present around the eyes and external nares. At necropsy, serous to catarrhal exudate may be present in the nasal passages, trachea, and major airways. In animals with profuse viscid exudate in the airways, there may be patchy vesicular to bullous emphysema in the lungs. Early pulmonary lesions are usually manifested as pinpoint gray lesions. As peripheral bronchiolectasis becomes apparent, varying sized foci are present with clear mucous- or pus-filled lumina. Affected lobes and areas are usually cranioventral in distribution, unilateral or bilateral, often asymmetric in severity, and dark plum­colored to light tan (Fig. 2.22). One or both tympanic bullae may contain serous to inspissated purulent mate­rial, with thickening of the tympanic membrane. The uterine horns, ovarian bursae, and oviducts may contain purulent exudate, but involvement of these sites may only be confirmed microscopically. Disseminated

FIG. 2.22. Chronic respiratory disease in a rat associated with Mycoplasma pulmonis infection. Note the asymmetric involvement of lung lobes and the irregular surface of affected areas due to bronchiolectasis and peribronchiolar lymphocytic infiltration.

FIG. 2.23. Bilateral swelling of tibiotarsal joints in a young rat with

naturally acquired systemic Mycoplasma pulmonis infection. Arthritis is a rare component of mycoplasmosis in the rat.

infection may occasionally result in arthritis, with swell­ing of the tibiotarsus (Fig. 2.23).

Microscopic changes in the affected tympanic bullae, turbinates, and major airways are characterized by a leukocytic infiltrate in the submucosa consisting of neu­trophils, lymphocytes, and plasma cells.

FIG. 2.24. Peribronchiolar cuffing with lymphocytes and plasma cells, a characteristic feature of Mycoplasma pulmonis infection in rats.

FIG. 2.25. Pulmonary lesions associated with an advanced case of mycoplasmosis. There is marked bronchiolectasis, rupture of airways, and abscessation.

focal to segmental in distribution. Macrophages, neu­trophils, and mucus may be present in alveolar spaces, with lymphocytic infiltration in the alveolar septa. There may be variable degrees of alveolar emphysema, with focal to patchy rupture of alveolar septa. Genital tract lesions, when present, consist of perioophoritis and endometritis, with mononuclear and polymorpho­nuclear cell infiltration in the stratum compactum and endometrium. In some cases, the lumen may be packed with leukocytes. Inflammatory lesions may also arise in the male genital tract.

Diagnosis

CRD caused by M. pulmonis, CAR bacillus, or both has similar macroscopic and microscopic features. The role of CAR bacillus can be confirmed as already described.

FIG. 2.26. Chronic bronchiolitis associated with murine respiratory mycoplasmosis. Note the squamous metaplasia of respiratory epithelium, loss of cilia, and necrotic cellular debris filling the lumen.

Mycoplasma organisms are not readily visible microscop­ically, but their presence may be inferred by lack of cilia on respiratory epithelium. Mycoplasma pulmonis can usually be cultured from nasopharyngeal washes or affected sites such as the upper and lower respiratory tract and uterus using appropriate media, and can also be detected by PCR or immunohistochemistry. Cultures may fail to detect the organism in some infected ani­mals. Serology is commonly used for surveillance within a population. However, animals may be falsely sero­positive due to exposure to M. arthritidis. In addition, rats naturally exposed to M. pulmonis may be sero­negative for up to 4 months postexposure. Thus, there are limitations to relying solely on serology to confirm the diagnosis. The collection of tissues and sera from retired breeders is recommended as a useful means of screening for mycoplasmal infections. Serological test­ing for antibodies against coinfecting respiratory viruses such as Sendai virus, PVM, and rat coronavirus are recommended, particularly when lower respiratory dis­ease is severe. These agents can have an additive effect on the progression of CRD. Cultures for conventional bac­teria are critical, since there may be concurrent infec­tions with other bacteria, such as Pasteurella pneumotropica or Streptococcus pneumoniae. Infection should be considered chronic, with no merit in anti­biotic treatment other than palliating clinical signs. Differential diagnoses include pulmonary abscessation due to Corynebacterium kutscheri infection, chronic res­piratory infections due to the CAR bacillus, otitis media due to conventional bacteria, and suppurative metritis due to P. pneumotropica infection.