Cyclophosphamide and prednisolone exacerbate the severity of intestinal paratuberculosis in Mycobacterium paratuberculosis monoassociated mice

Abstract

In this study we examined the effects of continuous oral administration of the immunosuppressive agents cyclophosphamide and prednisolone on the susceptibility of gnotobiotic nu/+ BALB/c mice to intestinal paratuberculosis. Treatment with either cyclophosphamide or prednisolone led to fecal shedding of Mycobacterium paratuberculosis, and increased the numbers of M. paratuberculosis recovered from the intestinal tract and liver, to levels similar to those recovered from untreated nu/nu mice. Numerous acid-fast bacilli and granulomas were observed within the intestinal tracts and livers of cyclophosphamide and prednisolone treated nu/+ and untreated nu/nu mice. In contrast, untreated control nu/+ mice infrequently shed small numbers of bacilli, harbored low numbers of M. paratuberculosis in their intestinal tracts, and did not have visible granulomas and acid fast bacilli in their tissues. Spleen cells from cyclophosphamide and prednisolone treated nu/+ mice, and from untreated nu/nu mice, had a reduced ability to proliferate in vitro in response to mitogen and antigens. These observations are consistent with previous evidence that cellular immunity restricts the development of intestinal paratuberculosis.