Characterization of the bovine salivary gland transcriptome associated with Mycobacterium avium subsp. paratuberculosis experimental challenge

Sanjay Mallikarjunappa,Mounir Adnane,Niel A Karrow,Paul Cormican,Kieran G Meade

doi:10.1186/s12864-019-5845-4

Abstract

BackgroundMycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease is spread between cattle via the fecal-oral route, yet the functional changes in the salivary gland associated with infection remain uncharacterized. In this study, we hypothesized that experimental challenge with MAP would induce stable changes in gene expression patterns in the salivary gland that may shed light on the mucosal immune response as well as the regional variation in immune capacity of this extensive gland. Holstein-Friesian cattle were euthanized 33 months’ post oral challenge with MAP strain CIT003 and both the parotid and mandibular salivary glands were collected from healthy control (n = 5) and MAP exposed cattle (n = 5) for histopathological and transcriptomic analysis.ResultsA total of 205, 21, 61, and 135 genes were significantly differentially expressed between control and MAP exposed cattle in dorsal mandibular (M1), ventral mandibular (M2), dorsal parotid (P1) and ventral parotid salivary glands (P2), respectively. Expression profiles varied between the structurally divergent parotid and mandibular gland sections which was also reflected in the enriched biological pathways identified. Changes in gene expression associated with MAP exposure were detected with significantly elevated expression of BoLA DR-ALPHA, BOLA-DRB3 and complement factors in MAP exposed cattle. In contrast, reduced expression of genes such as polymeric immunoglobin receptor (PIGR), TNFSF13, and the antimicrobial genes lactoferrin (LF) and lactoperoxidase (LPO) was detected in MAP exposed animals.ConclusionsThis first analysis of the transcriptomic profile of salivary glands in cattle adds an important layer to our understanding of salivary gland immune function. Transcriptomic changes associated with MAP exposure have been identified including reduced LF and LPO. These critical antimicrobial and immunoregulatory proteins are known to be secreted into saliva and their downregulation may contribute to disease susceptibility. Future work will focus on the validation of their expression levels in saliva from additional cattle of known infection status as a potential strategy to augment disease diagnosis.

Highlights

Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease is spread between cattle via the fecal-oral route, yet the functional changes in the salivary gland associated with infection remain uncharacterized
By performing transcriptomic analysis of salivary glands, we identified differentially expressed immune-related genes in cattle challenged with MAP
Studies designed to observe the host response to MAP infection in cattle have mostly focused on intestinal immune response where MAP gains entry from intestinal mucosa into submucosal gut-associated lymphoid tissues (GALT), such as the ileal Peyer’s patches after its ingestion through fecal-oral route [23]

Summary

Introduction

Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease is spread between cattle via the fecal-oral route, yet the functional changes in the salivary gland associated with infection remain uncharacterized. Paratuberculosis (MAP), the etiologic agent of Johne’s disease is spread between cattle via the fecal-oral route, yet the functional changes in the salivary gland associated with infection remain uncharacterized. Paratuberculosis (MAP) is the etiological agent of Johne’s disease (JD) in cattle. The fecal-oral route is the primary mode of MAP transmission and calves less than 6 months of age are known to be highly susceptible to MAP infection [1, 2] The pathogenesis of JD involves a long latent subclinical phase and a symptomatic clinical phase. Asymptomatic, shedding of MAP occurs intermittently during the sub-clinical phase causing disease dissemination. During the clinical phase, infected animals present with profuse watery diarrhea, loss of weight and a significant reduction in milk production, eventually causing wasting and death [3]. Whether MAP can cause Crohn’s disease is controversial and debatable, isolation of MAP from the intestines of patients suffering from Crohn’s disease has raised public health concerns [5]

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