Embracing nature’s complexity: Immunoparasitology in the wild

Mair, Iris; McNeilly, Tom N.; Corripio-Miyar, Yolanda; Forman, Ruth; Else, Kathryn J.

doi:10.1016/j.smim.2021.101525

Cited by 6 publications

(8 citation statements)

References 142 publications

(142 reference statements)

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“…According to previous research, in agreement with the adaptive immune response of the green module, following the initiation of a cellmediated immune response, the initiation of humoral immunity specially B-cell-dependent signals, such as "B cell receptor signaling pathway" during M. bovis infection, may be involved in the mycobactericidal response in bTB (Pollock et al, 2006;Aranday-Cortes et al, 2012). Interestingly, most of the hub-central genes in the green module, including CD3E (Mair et al, 2021), ZAP70 (Samten et al, 2009), CD4 (Boggiatto et al, 2021), IL2RA (Lu et al, 2011), CD247, LCK, CD3D, CD3G, PRKCQ (McLoughlin et al, 2021a, and ITK (Huang et al, 2020), were closely related to T-cell activation and the host immune response to infection with MTBC intracellular pathogens. The CD3E hub-central gene is an essential core for T-cell activation (Mair et al, 2021) and plays a crucial role in the immune response against TB (Gebremicael et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Interestingly, most of the hub-central genes in the green module, including CD3E ( Mair et al, 2021 ), ZAP70 ( Samten et al, 2009 ), CD4 ( Boggiatto et al, 2021 ), IL2RA ( Lu et al, 2011 ), CD247 , LCK , CD3D , CD3G , PRKCQ ( McLoughlin et al, 2021a ), and ITK ( Huang et al, 2020 ), were closely related to T-cell activation and the host immune response to infection with MTBC intracellular pathogens. The CD3E hub-central gene is an essential core for T-cell activation ( Mair et al, 2021 ) and plays a crucial role in the immune response against TB ( Gebremicael et al, 2019 ). Based on the results of previous research, an intense decrease in the expression of CD3E in patients with active TB and then an increase in the expression of this gene during the treatment period exhibited that this gene has a negative correlation with the progression of mycobacterial infection ( Jenum et al, 2016 ; Gebremicael et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

et al. 2022

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ObjectiveBovine tuberculosis (bTB) is a chronic respiratory infectious disease of domestic livestock caused by intracellular Mycobacterium bovis infection, which causes ~$3 billion in annual losses to global agriculture. Providing novel tools for bTB managements requires a comprehensive understanding of the molecular regulatory mechanisms underlying the M. bovis infection. Nevertheless, a combination of different bioinformatics and systems biology methods was used in this study in order to clearly understand the molecular regulatory mechanisms of bTB, especially the immunomodulatory mechanisms of M. bovis infection.MethodsRNA-seq data were retrieved and processed from 78 (39 non-infected control vs. 39 M. bovis-infected samples) bovine alveolar macrophages (bAMs). Next, weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression modules in non-infected control bAMs as reference set. The WGCNA module preservation approach was then used to identify non-preserved modules between non-infected controls and M. bovis-infected samples (test set). Additionally, functional enrichment analysis was used to investigate the biological behavior of the non-preserved modules and to identify bTB-specific non-preserved modules. Co-expressed hub genes were identified based on module membership (MM) criteria of WGCNA in the non-preserved modules and then integrated with protein–protein interaction (PPI) networks to identify co-expressed hub genes/transcription factors (TFs) with the highest maximal clique centrality (MCC) score (hub-central genes).ResultsAs result, WGCNA analysis led to the identification of 21 modules in the non-infected control bAMs (reference set), among which the topological properties of 14 modules were altered in the M. bovis-infected bAMs (test set). Interestingly, 7 of the 14 non-preserved modules were directly related to the molecular mechanisms underlying the host immune response, immunosuppressive mechanisms of M. bovis, and bTB development. Moreover, among the co-expressed hub genes and TFs of the bTB-specific non-preserved modules, 260 genes/TFs had double centrality in both co-expression and PPI networks and played a crucial role in bAMs-M. bovis interactions. Some of these hub-central genes/TFs, including PSMC4, SRC, BCL2L1, VPS11, MDM2, IRF1, CDKN1A, NLRP3, TLR2, MMP9, ZAP70, LCK, TNF, CCL4, MMP1, CTLA4, ITK, IL6, IL1A, IL1B, CCL20, CD3E, NFKB1, EDN1, STAT1, TIMP1, PTGS2, TNFAIP3, BIRC3, MAPK8, VEGFA, VPS18, ICAM1, TBK1, CTSS, IL10, ACAA1, VPS33B, and HIF1A, had potential targets for inducing immunomodulatory mechanisms by M. bovis to evade the host defense response.ConclusionThe present study provides an in-depth insight into the molecular regulatory mechanisms behind M. bovis infection through biological investigation of the candidate non-preserved modules directly related to bTB development. Furthermore, several hub-central genes/TFs were identified that were significant in determining the fate of M. bovis infection and could be promising targets for developing novel anti-bTB therapies and diagnosis strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

et al. 2022

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“…The use of mice models such as the rewilding mice model has helped us appreciate the critical role the host environment can play in outcomes during T. muris infection (147,149). However, there is still a need to understand how the tissue microenvironment (3) and/or host macroenvironment (142,150) can influence susceptibility patterns and helminth infection outcomes during exposure to various other helminth parasite types (hookworms, roundworms, tapeworms). New environmental mouse models such as "rewildings", "wildlings", "co-housing", "sequential infection models", "co-infection models", "chimeric wild mouse" etc (142,146,(151)(152)(153) provide new opportunities to understand the role of environmental factors in influencing susceptibility to infection and re-infection by helminth parasite.…”

Section: Role Of Environment During Helminth Induced Type 2 Immune Re...mentioning

confidence: 99%

The Influence of Genetic and Environmental Factors and Their Interactions on Immune Response to Helminth Infections

2022

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Helminth infection currently affect over 2 billion people worldwide, with those with the most pathologies and morbidities, living in regions with unequal and disproportionate access to effective healthcare solutions. Host genetics and environmental factors play critical roles in modulating and regulating immune responses following exposure to various pathogens and insults. However, the interplay of environment and genetic factors in influencing who gets infected and the establishment, persistence, and clearance of helminth parasites remains unclear. Inbred strains of mice have long been used to investigate the role of host genetic factors on pathogenesis and resistance to helminth infection in a laboratory setting. This review will discuss the use of ecological and environmental mouse models to study helminth infections and how this could be used in combination with host genetic variation to explore the relative contribution of these factors in influencing immune response to helminth infections. Improved understanding of interactions between genetics and the environment to helminth immune responses would be important for efforts to identify and develop new prophylactic and therapeutic options for the management of helminth infections and their pathogenesis.

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“…Unsurprisingly, the immune system of 'naïve' adult laboratory mice resembles that of human newborns more than that of human adults (1). It is therefore important to cross-validate laboratory models within ecologically relevant frameworks, and delineate associations in complex, natural systems that may not be possible to be recapitulated in the laboratory setting (2). Indeed, there are now multiple reports pointing to wider environmental influences being critical in determining infection outcome and health impacts of experimental infections (3,4).…”

Section: Introductionmentioning

confidence: 99%

The adaptive immune response toTrichurisin wild versus laboratory mice: An established model system in context

Mair,

Fenn,

Wolfenden

et al. 2023

Preprint

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Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipwormTrichuris murisbetween controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing worm burden was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wildM.m.domesticus,there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to ‘real world’ immune function.

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Embracing nature’s complexity: Immunoparasitology in the wild

Abstract: Graphical abstract

Cited by 6 publications

References 142 publications

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

The Influence of Genetic and Environmental Factors and Their Interactions on Immune Response to Helminth Infections

The adaptive immune response toTrichurisin wild versus laboratory mice: An established model system in context

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