Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Wed, 05 Dec 2018 08:35:36 J. Med. Microbiol. - Vol. 47 (1998), 725-731 [c 1998 The Pathological Society of Great Britain and Ireland BACTE R I AL PATH 0 G EN I CITY Mycobacterium avium infection of gut mucosa in mice associated with late inflammatory response and intestinal cell necrosis S. Y. KIM, J. R. GOODMAN*, MARY PETROFSKY and L. E. BERMUDEZ Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, CA 94 I 75 and *Department of Pediatric Electron Microscopy, University of California San Francisco, San Francisco, CA 94143, USA Mycobacterium avium is an intracellular pathogen that ‘is associated with disseminated infection in acquired immunodeficiency syndrome (AIDS). Patients with AIDS appear to acquire M. avium mainly through the gastrointestinal tract. Previous studies have shown that healthy mice given M. avium orally develop disseminated infection after 2-4 weeks. The chief site of M. avium invasion of the intestinal mucosa is the terminal ileum. To learn more about the pathophysiology of M. avium infection of the intestinal mucosa, C57BL/6 bg+ bg+ mice were infected orally with M. avium strain 101 and groups of six mice were killed each week for 8 weeks. The terminal ileum was then prepared for histopathological studies and electron microscopy. A delayed inflammatory response was observed and influx of neutrophils in the Peyer’s patches was the only abnormality seen at 1 week. A severe inflammatory response was seen from week 2 to week 5 and necrosis of intestinal villi was observed 6 weeks after infection. These results indicate that invasion and infection of the normal intestine by M. avium results in a severe inflammatory response with segmental necrosis of the intestinal mucosa. Introduction Mycobacterium avium is an intracellular pathogen that can cause disseminated infection in patients with acquired immunodeficiency syndrome (AIDS), as well as in patients with other long-term immunosuppressive diseases [ 1-31. In AIDS patients, M. avium infection is mainly acquired through the gastrointestinal tract [4] although the respiratory tract has been described as the route of infection in a small percentage of patients [5]. Some studies have shown that colonisation of the gastrointestinal tract precedes the isolation of M. avium in blood and tissues by weeks to months [6]. Recent studies have demonstrated that M. avium is capable of invading intestinal mucosal cells in vitro [7, 81 and the intestinal mucosa of healthy mice in vivo [9]. The ability to enter the intestinal mucosa in vivo was strain-dependent. It was observed that the preferential sites of M. avium entry were the terrninal ileum and the ascending colon [9] suggesting that the Peyer’s patches are involved in the process of M. avium uptake. Histopathological studies of intestines of AIDS patients with disseminated M. avium infection have shown a large number of organisms in the mucosal epithelial cells and in the lamina propria of the intestines, usually within macrophages [lo]. M. aviurn within regional lymph nodes is commonly observed in autopsy studies [ 10, 1 13. Despite these recent findings, little is known about the pathogenesis of M. avium infection of the intestinal tract in AIDS. Therefore, to better understand the Table 1. Number of M. avium in the terminal ileum of beige mice at several weeks after oral infection Weeks* Mean (SEM) number of bacteria/g of tissue 2.4 (0.5) X lo3 6.1 (0.6) X lo5 1.1 (0.4) X lo6 4.7 (0.4) x 104 3.5 (0.7) x 107 Received 22 July 1997; accepted 17 Dec. 1997. Corresponding author: Dr L. E. Bermudez. ~~ *Mice were infected orally with 5 X lo8 bacteria. Control mice (given buffer instead) showed no evidence of M. avium infection.