Characterization of a Murine Model ofUreaplasma urealyticumPneumonia

Abstract

Ureaplasma urealyticum respiratory tract colonization in preterm infants has been associated with a high incidence of pneumonia and the development of bronchopulmonary dysplasia. However, study of this human pathogen has been hampered by the absence of animal models. We have developed the first juvenile mouse model of Ureaplasma pneumonia and characterized the histopathology during the month following inoculation. C3H/ HeN mice were inoculated intratracheally with a mouse-adapted clinical Ureaplasma isolate (biovar 2) or sham inoculated with 10B broth. Culture of lung homogenates and PCR of DNA from bronchoalveolar lavage fluid (BAL) confirmed the presence of Ureaplasma in 100% of inoculated animals at 1 day, 60% at 2 days, 50% at 3 days, and 25% at 7 and 14 days. Ureaplasma was undetectable 28 days postinoculation. There were marked changes in BAL and interstitial-cell composition with increased number of polymorphonuclear leukocytes 1 to 2 days and 14 days postinoculation and macrophages at 2 and 14 days postinoculation. The Ureaplasma infection caused a persistent focal loss of airway ciliated epithelium and a mild increase in interstitial cellularity. There were no differences in BAL protein concentration during the first 28 days, suggesting that pulmonary vascular endothelial barrier integrity remained intact. Comparison of BAL cytokine and chemokine concentrations revealed low levels of tumor necrosis factor alpha (TNF-␣) at 3 days and monocyte chemoattractant protein 1 at 7 days in Ureaplasma-infected mice but a trend toward increased TNF-␣ at 14 days and increased granulocyte-macrophage colony-stimulating factor and interleukin-10 at 28 days. These data suggest that Ureaplasma alone may cause limited inflammation and minimal tissue injury in the early phase of infection but may promote a mild chronic inflammatory response in the later phase of infection (days 14 to 28), similar to the process that occurs in human newborns.

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

“…Coalson's group has previously noted an increase in alveolar macrophages in a baboon model of prematurity and infection with U. urealyticum (20). Our data are also compatible with those reported in a murine model of U. urealyticum infection in which an initial airway neutrophilia was followed by increased airway macrophages (21). Studies of postmortem lungs by Viscardi's group showed that alveolar macrophages predominated when the infants were colonized with U. Urealyticum but with airway neutrophilia when they were not (22).…”

Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice

“…Studies show that colonization of the reproductive tract is commonly associated with infertility, abortions, premature births and lung injury in neonates (Ruhnke et al 1984, Murray 1991, Buzinhani et al 2011. In other mycoplasma species, such as U. urealyticum, was observed that the presence of bacteria in the respiratory tract of infants stimulates an increasing total number of white blood cells (Viscardi et al 2002). However, the observed leukocytosis is associated with low immunity (Tegtmeier et al 1999, Ohlsson et al 1993, Honma et al 2007).…”

“…Ultra-structural changes were observed with reduction of microvilli in the endometrial epithelial cells (McGowin et al 2013). However, for Ureaplasma ssp., histological alterations are mostly related to chronic fetal infections (Robinson et al 2013) or other body sites as lung (Viscardi et al 2002). Although this study did not assess the progression of later periods, this model of infection by U. diversum does not induce an acute infl ammatory response in healthy animals.…”

Intradermal Immunization of BALB/C Mice with Heat Killed Klebsiella pneumoniae ATCC BAA1706 Leads to the Production of both IgG1 and IgG2a

“…The mice were anesthetized with intraperitoneal xylazine and ketamine solution inoculum (ketamine 100 mg/kg; xylazine 12 mg/kg). Then we performed the intratracheal inoculum of 50µL of the bacterial solution or sterile saline as adapted from Viscardi (Viscardi et al, 2002). 24 hours after challenge, the animals were euthanized by overdosage of ketamine and xylazine.…”