Bacterial and viral pathogen-associated molecular patterns induce divergent early transcriptomic landscapes in a bovine macrophage cell line

Toka, Felix N.; Dunaway, Kiera; Smaltz, Felicia; Szulc-Dąbrowska, Lidia; Drnevich, Jenny; Mielcarska, Matylda Barbara; Bossowska-Nowicka, Magdalena; Schweizer, Matthias

doi:10.1186/s12864-018-5411-5

Cited by 7 publications

(7 citation statements)

References 55 publications

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“…It is well established that PRRs are usable for detecting pathogen-associated molecular patterns (55). PRRs signal through a diverse array of intermediate molecular adaptors to activate transcription factors that drive gene transcription responsible for antimicrobial activity (56). Recognition of microbial nucleic acids by endosomal or cytosolic PRRs constitutes a key component in the innate immune system to combat invading bacterial and viral pathogens (57).…”

Section: Discussionmentioning

confidence: 99%

Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

et al. 2020

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Exclusive breastfeeding impacts the intestinal microbiome and is associated with a better immune function than is seen with milk formula (MF) feeding in infants and yet with mechanisms poorly defined. The porcine model was used to evaluate the impact of MF on ileum microbial communities and gene expression relative to human milk (HM)-fed piglets. Fifty-two Dutch Landrace male piglets were fed an isocaloric diet of either HM (n = 26) or MF (n = 26) from day 2 through day 21 of age and weaned to a solid diet until day 51. Eleven piglets from each group were euthanized at day 21, while the remaining piglets (HM, n = 15; MF, n = 15) were euthanized at day 51 to collect ileal epithelium (EP) scrapings and ileal (IL) tissues. The epithelial mucosa was subjected to shotgun metagenome sequencing, and EP and IL tissues were used for transcriptome analysis. On day 21, transcriptome data revealed that the levels of pathways involved in inflammation and apoptosis were significantly higher in MF piglets than in HM piglets, whereas the levels of tight junctions and pathogen detection systems were lower in MF piglets than in HM piglets. The MF impacts on the small intestine were maintained over the postweaning period (day 51) as indicated by higher levels of Dialister invisus bacteria and higher levels of expression of genes associated with inflammation and apoptosis pathways relative to HM group. The current study demonstrated that MF might impact local intestinal inflammation, apoptosis, and tight junctions and might suppress pathogen recognition in the small intestine compared with HM. IMPORTANCE Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended to improve health outcomes during early life and beyond. When women are unable to provide sufficient HM, milk formula (MF) is often recommended as a complementary or alternative source of nutrition. Previous studies in piglets demonstrated that MF alters the gut microbiome and induces inflammatory cytokine production. The links between MF feeding, gut microbiome, and inflammation status are unclear due to challenges associated with the collection of intestinal samples from human infants. The current report provides the first insight into MF-microbiome-inflammation connections in the small intestine compared with HM feeding using a porcine model. The present results showed that, compared with HM, MF might impact immune function through the induction of ileal inflammation, apoptosis, and tight junction disruptions and likely compromised immune defense against pathogen detection in the small intestine relative to piglets that were fed HM.

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Section: Discussionmentioning

confidence: 99%

Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

et al. 2020

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“…Transcription profiles of macrophages infected with several types of bacteria and bacterial and viral ligands have been studied earlier (Lewandowska-Sabat et al, 2013; Nalpas et al, 2013; Casey et al, 2015; Mavromatis et al, 2015; Hop et al, 2017; Roy et al, 2018; Toca et al, 2019). To the best of our knowledge, this is the first study of the early-phase transcriptome of bMDMs infected in vitro with two strains of S. agalactiae .…”

Section: Discussionmentioning

confidence: 99%

Transcription Profiling of Monocyte-Derived Macrophages Infected In Vitro With Two Strains of Streptococcus agalactiae Reveals Candidate Pathways Affecting Subclinical Mastitis in Cattle

et al. 2019

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Macrophages are key cells of innate immune response and serve as the first line of defense against bacteria. Transcription profiling of bacteria-infected macrophages could provide important insights on the pathogenicity and host defense mechanisms during infection. We have examined transcription profiles of bovine monocyte-derived macrophages (bMDMs) isolated from the blood of 12 animals and infected in vitro with two strains of Streptococcus agalactiae . Illumina sequencing of RNA from 36 bMDMs cultures exposed in vitro to either one of two sequence types of S. agalactiae (ST103 or ST12) for 6 h and unchallenged controls was performed. Analyses of over 1,656 million high-quality paired-end sequence reads revealed 5,936 and 6,443 differentially expressed genes ( p < 0.05) in bMDMs infected with ST103 and ST12, respectively, versus unchallenged controls. Moreover, 588 genes differentially expressed between bMDMs infected with ST103 versus ST12 were identified. Ingenuity pathway analysis of the differentially up-regulated genes in the bMDMs infected with ST103 revealed significant enrichment for granulocyte adhesion and diapedesis, while significant enrichment for the phagosome formation pathway was found among down-regulated genes. Moreover, Ingenuity pathway analysis of the differentially up-regulated genes in the bMDMs infected with ST12 showed significant enrichment for type 1/type 2 T helper cell activation, while the complement activation pathway was overrepresented in the down-regulated genes. Our study identified pathogen-induced regulation of key genes and pathways involved in the immune response of macrophages against infection but also likely involved in bacterial evasion of the host immune system. These results may contribute to better understanding of the mechanisms underlying subclinical infection such as bovine streptococcal mastitis.

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“…As an approach to integrate the previous results, we conducted an IPA evaluation. IPA has previously shown its capacity to identify innate immune signaling pathways in macrophages stimulated with mycobacteria [36] and those that involve pattern-recognizing molecular components [37]. The IPA analysis showed similar biological interactions induced by M.BCG and P.BCG.…”

Section: Discussionmentioning

confidence: 85%

RNA Microarray-Based Comparison of Innate Immune Phenotypes between Human THP-1 Macrophages Stimulated with Two BCG Strains

Molina-Olvera

Rivas-Ortiz

Schcolnik‐Cabrera

et al. 2022

IJMS

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Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient’s age and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico (M.BCG) or Phipps (P.BCG) strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN-I) and IFN-γ. However, four DEGs were identified in macrophages infected with M.BCG compared to P. BCG. These findings indicated the proinflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression, suggesting a differential expression pattern of innate immune transcripts depending on the mycobacterial strain.

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Bacterial and viral pathogen-associated molecular patterns induce divergent early transcriptomic landscapes in a bovine macrophage cell line

Cited by 7 publications

References 55 publications

Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model

Transcription Profiling of Monocyte-Derived Macrophages Infected In Vitro With Two Strains of Streptococcus agalactiae Reveals Candidate Pathways Affecting Subclinical Mastitis in Cattle

RNA Microarray-Based Comparison of Innate Immune Phenotypes between Human THP-1 Macrophages Stimulated with Two BCG Strains

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