Proliferative Typhlocolitis With Multinucleated Giant Cells: A Nonspecific Enteropathy in Immunodeficient Sentinel Mice

Abstract

Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and high-security facilities presented to the Comparative Pathology Laboratory (CPL) with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether clinical signs were present or absent, the gross observation of ceco-colonic thickening corresponded histologically to pleocellular typhlocolitis with mucosal hyperplasia and lamina proprial multinucleated cells. A subset of affected sentinels exhibited granulomatous serositis and hepatosplenic necrosis with multinucleated cells. Initial suspicion of mouse hepatitis virus infection was excluded by polymerase chain reaction, electron microscopy, and serology. Multinucleated giant cells were confirmed as macrophages by positive immunoreactivity to Mac-3 and Iba-1 and negative immunoreactivity to pancytokeratin. From conventional and medium-security facilities, Helicobacter species were identified in 40 of 143 (27.9%) mice, with H. hepaticus accounting for 72.5% of identified Helicobacter species. Other agents included opportunistic bacterial infection (41/145, 28.3%), murine norovirus (16/106, 15.1%), and pinworms (2/146, 1.4%). From high-security facilities, only Enterobacter cloacae was identified (2/13, 15.4%), and no evidence of Helicobacter sp., murine norovirus, or pinworms was present. No potentially infectious disease agent(s) was identified in 71 of 146 (48.6%) affected nude sentinels from conventional and medium-security facilities and 11 of 13 (84.6%) affected nude sentinels from high-security facilities. No statistically significant differences in histologic lesion scores were identified between Helicobacter-positive and Helicobacter-negative mice. Thus, proliferative typhlocolitis with multinucleated giant cells was considered a nonspecific histologic pattern associated with a variety of primary and opportunistic pathogens in athymic nude mice.

Review: Other Helicobacter species

“…41 Eimeria parasite coccidiosis is an economically important disease of poultry and livestock worldwide. 43 While Helicobacter species were identified in 40 of 143 mice, with H. hepaticus accounting for 72.5% of the identified Helicobacter species, this H. hepaticus-associated enteropathy was not specific. 42 Proliferative typhlocolitis with multinucleated giant cells was observed in immunodeficient sentinel mice from conventional and medium-security facilities.…”

“…42 Proliferative typhlocolitis with multinucleated giant cells was observed in immunodeficient sentinel mice from conventional and medium-security facilities. 43 While Helicobacter species were identified in 40 of 143 mice, with H. hepaticus accounting for 72.5% of the identified Helicobacter species, this H. hepaticus-associated enteropathy was not specific. 43…”

“…43 While Helicobacter species were identified in 40 of 143 mice, with H. hepaticus accounting for 72.5% of the identified Helicobacter species, this H. hepaticus-associated enteropathy was not specific. 43…”

“…Enterobacteriaceae and Helicobacter load were increased in the gut of BALB/c mice infected with the Eimeria falciformis parasite. 43 43 While Helicobacter species were identified in 40 of 143 mice, with H. hepaticus accounting for 72.5% of the identified Helicobacter species, this H. hepaticus-associated enteropathy was not specific.…”

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

“…Until now, at least nine distinct Helicobacter species (namely, H. hepaticus, H. typhlonius, H. bilis, H. rodentium, H. ganmani, H. muridarum, H. mastomyrinus, H. rappini, H. trogontium ) were isolated from the gastrointestinal tract of laboratory rodents, which is why co-infections are not uncommon and may worsen disease development [ 83 , 84 , 85 ]. Since most genetically modified immunodeficient mouse and rat strains lack sufficient pathogen defense mechanisms, those animals are generally prone to develop infectious diseases and, as a result, unspecific intestinal inflammation may spontaneously occur after exposure to mixed opportunistic agents [ 86 ]. For the same reasons, immunodeficient rodents may develop other pathologies after infection with microorganisms, which are generally not harmful to immunocompetent animals.…”