WC1+ and WC1neg γδ T lymphocytes in intestinal mucosa of healthy and Mycobacterium avium subspecies paratuberculosis-infected calves

Ludwig, Latasha; Egan, Rebecca; Baquero, Monica; Mansz, Amanda; Plattner, Brandon L.

doi:10.1016/j.vetimm.2019.109919

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…Data presented are for cytokine genes showing differential (*p < 0.05) gene expression in MAP-infected segments relative to PBS control segments at 2 months post-infection, in addition to those cytokine genes that were identified as differentially expressed at 12 months post-infection (Figure 6). (61,66), and there is a greater capacity for the induction of mucosal immune responses (34).…”

Section: Discussionmentioning

confidence: 99%

Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent Mycobacterium avium ssp. paratuberculosis Infection

Facciuolo

Lee

Cano³

et al. 2020

Front. Immunol.

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Chronic enteric Mycobacterium avium ssp. paratuberculosis (MAP) infections are endemic in ruminants globally resulting in significant production losses. The mucosal immune responses occurring at the site of infection, specifically in Peyer's patches (PP), are not well-understood. The ruminant small intestine possesses two functionally distinct PPs. Discrete PPs function as mucosal immune induction sites and a single continuous PP, in the terminal small intestine, functions as a primary lymphoid tissue for B cell repertoire diversification. We investigated whether MAP infection of discrete vs. continuous PPs resulted in the induction of significantly different pathogen-specific immune responses and persistence of MAP infection. Surgically isolated intestinal segments in neonatal calves were used to target MAP infection to individual PPs. At 12 months post-infection, MAP persisted in continuous PP (n = 4), but was significantly reduced (p = 0.046) in discrete PP (n = 5). RNA-seq analysis revealed control of MAP infection in discrete PP was associated with extensive transcriptomic changes (1,707 differentially expressed genes) but MAP persistent in continuous PP elicited few host responses (4 differentially expressed genes). Cytokine gene expression in tissue and MAP-specific recall responses by mucosal immune cells isolated from PP, lamina propria and mesenteric lymph node revealed interleukin (IL)22 and IL27 as unique correlates of protection associated with decreased MAP infection in discrete PP. This study provides the first description of mucosal immune responses occurring in bovine discrete jejunal PPs and reveals that a significant reduction in MAP infection is associated with specific cytokine responses. Conversely, MAP infection persists in the continuous ileal PP with minimal perturbation of host immune responses.Facciuolo et al. Mucosal Immunity Controlling MAP InfectionThese data reveal a marked dichotomy in host-MAP interactions within the two functionally distinct PPs of the small intestine and identifies mucosal immune responses associated with the control of a mycobacterial infection in the natural host.

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Section: Discussionmentioning

confidence: 99%

Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent Mycobacterium avium ssp. paratuberculosis Infection

Facciuolo

Lee

Cano³

et al. 2020

Front. Immunol.

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“…In contrast, at the LP level, where the lesions progress in diffuse forms, the number of positively immunolabelled Foxp3 + T cells observed was very low. This suggests a suppression or destruction of these cells in this intestinal area caused by other regulatory T subsets [34,35], by speci c cytokines, such as IL-10 or TGF-β, produced by certain of helper T lymphocytes subsets [36], by the macrophages that make up the diffuse granulomatous in ltrate present in LP [37,38] or by the Foxp3 + T cells themselves [16].…”

Section: Discussionmentioning

confidence: 99%

Local Assessment of the Immunohistochemical Expression of Foxp3+ Regulatory T Lymphocytes in the Different Pathological Forms Associated with Bovine Paratuberculosis

Zapico

Espinosa

Criado

et al. 2022

Journal of Comparative Pathology

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“…The extent of protection afforded by γδ T cells responses to MAP infection in vivo is undetermined. Persistent MAP infection in CPP of young calves promoted a local accumulation of the WC1 + subset of γδ T cells, decreased the WC1 neg subset in the intestinal epithelium, and increased the total γδ T cells in lamina propria at 7 months post-infection ( 39 ). In the present study, we did not investigate specific γδ T cell subsets.…”

Section: Discussionmentioning

confidence: 99%

“…MAP strain gc86 (10 10 CFU; Supplementary Figure 1 ) was injected into the lumen of each intestinal segment. This strain is a low-passage Type II field isolate of MAP ( 37 ) previously used in calf infection studies ( 28 , 29 , 38 , 39 ). For each trial, a low-passage frozen stock of MAP strain gc86 was plated and a single colony inoculated into Difco™ Middlebrook 7H9 broth (BD and Company, USA) supplemented with 10% BBL™ Middlebrook OADC Enrichment (BD and Company, USA) and 2 mg/L ferric mycobactin J (Allied Monitor Inc., USA).…”

Section: Methodsmentioning

confidence: 99%

A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery

et al. 2020

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Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Mycobacteriumavium ssp. paratuberculosis (MAP) is an enteric pathogen that establishes a persistent, asymptomatic infection in the small intestine. Difficulty in reproducing infection in surrogate animal models and limited understanding of mucosal immune responses that control enteric infection in the natural host have been major barriers to MAP vaccine development. We previously developed a reproducible challenge model to establish a consistent MAP infection using surgically isolated intestinal segments prepared in neonatal calves. In the current study, we evaluated whether intestinal segments could be used to screen parenteral vaccines that alter mucosal immune responses to MAP infection. Using Silirum® – a commercial MAP bacterin – we demonstrate that intestinal segments provide a platform for assessing vaccine efficacy within a relatively rapid period of 28 days post-infection. Significant differences between vaccinates and non-vaccinates could be detected using quantitative metrics including bacterial burden in intestinal tissue, MAP shedding into the intestinal lumen, and vaccine-induced mucosal immune responses. Comparing vaccine-induced responses in mucosal leukocytes isolated from the site of enteric infection versus blood leukocytes revealed substantial inconsistences between these immune compartments. Moreover, parenteral vaccination with Silirum did not induce equal levels of protection throughout the small intestine. Significant control of MAP infection was observed in the continuous but not the discrete Peyer’s patches. Analysis of these regional mucosal immune responses revealed novel correlates of immune protection associated with reduced infection that included an increased frequency of CD335+ innate lymphoid cells, and increased expression of IL21 and IL27. Thus, intestinal segments provide a novel model to accelerate vaccine screening and discovery by testing vaccines directly in the natural host and provides a unique opportunity to interrogate mucosal immune responses to mycobacterial infections.

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WC1+ and WC1neg γδ T lymphocytes in intestinal mucosa of healthy and Mycobacterium avium subspecies paratuberculosis-infected calves

Cited by 14 publications

References 36 publications

Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent Mycobacterium avium ssp. paratuberculosis Infection

Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent Mycobacterium avium ssp. paratuberculosis Infection

Local Assessment of the Immunohistochemical Expression of Foxp3+ Regulatory T Lymphocytes in the Different Pathological Forms Associated with Bovine Paratuberculosis

A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery

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