CpG oligodeoxynucleotides promote phospholipase D dependent phagolysosome maturation and intracellular mycobacterial killing in M. tuberculosis infected type II alveolar epithelial cells

Greco, Emanuela A.; Santucci, Marilina B.; Quintiliani, Gianluca; Papi, Massimiliano; Spirito, Marco De; Fraziano, Maurizio

doi:10.1016/j.cellimm.2009.06.002

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…Because freshly explanted human alveolar type II cells are difficult to obtain, A549 cells are a useful surrogate for the study of respiratory epithelial cell responses at the level of the alveolus [29]. Of relevance to our study is the fact that these cells have been used to study the interaction of mycobacteria with respiratory epithelium [30]–[34]. Also relevant to our study are previous reports indicating that A549 cells express TLR2, express HβD2 in response to IL1-β and TLR2 stimulation [16], and express HβD2 in response to M. tuberculosis infection [35].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

et al. 2011

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Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL) expressing variant (smooth phenotype) in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs) which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8) and human β-defensin 2 (HβD2) are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2) receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with “masking” of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

et al. 2011

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“…Less clear is whether bronchial epithelial cells or type II alveolar epithelial cells express TLR9. Such expression was reported in two studies (Droemann et al, 2005;Greco et al, 2009), whereas other groups claim that these cells express little or no TLR9 and cannot respond to CpG ODN (Mayer et al, 2007;Pesce et al, 2010).…”

Section: Effect Of Cpg Odn On the Mucosal Immune Systemmentioning

confidence: 86%

Use of CpG Oligonucleotides as Mucosal Adjuvants

Gürsel

Klinman

2015

Mucosal Immunology

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“…During the last decade, CpG have been studied for their application in therapeutic and vaccine strategies, while are still limited the studies elucidating their stimulating role in the innate response to bacterial infections. These bacterial sequences are considered a type of Pathogen-Associated Molecular Pattern (PAMP) due to their abundance in bacterial genomes, and their immunostimulatory capacity against many intracellular pathogens, including Listeria monocytogenes, Leishmania major, Francisella tularensis, Klebsiella pneumonia [1][2][3][4][5][6] Staphylococcus aureus [7] and Mycobacterium tuberculosis (MTB) [8,[9][10][11] have been documented. Some studies were performed, primarily, to describe their adjuvant properties in mice, but few data are available on the eff ects of CpGs in humans.…”

Section: Introductionmentioning

confidence: 99%

A New CpG ODN Induces a Fine-Tuning of Innate Response Resulting in Mycobacterium tuberculosis Containment

Cappelli¹,

Giovannini²,

Basso³

et al. 2022

J Biomed Res Environ Sci

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Synthetic oligodeoxynucleotides containing bacterial CpG motifs trigger an immunomodulatory response that correlates with both the CpG hhhexamers and their flanking regions. In this study, four new phosphodiester backbone CpG ODNs were studied in the contest of the innate immune response to Mycobacterium tuberculosis (MTB) infection. Two out of the four CpG ODNs (CpG2 and CpG3) displayed significant and opposite immunomodulatory effects: CpG2 enhanced MTB containment by human Monocyte-Derived-Macrophages (MDM), while CpG3 promoted an increased pathogen growth, higher ROS and Labile Iron Pool (LIP) levels. Accordingly, for iron homeostasis genes transcription, CpG2 and CpG3 induced, respectively, an iron retention and iron release phenotype. Moreover, CpG2 induced NLRC4 and TRAF6 gene expression and repressed IKK alpha and TREM1 while CpG3 induced PPBP and IL-36 RN and repressed TRAF6, IL-1B, IL-1R2 and NF-kB2. After MTB infection, CpG2 increased the release of soluble TREM1 protein among many others as compared with fewer innate response-associated proteins induced by CpG3. We suggest that CpG2 helps the containment of MTB infection, by inducing an early tight balance of MDM activation players, including LIP, chemokines, ROS and TREM1 receptors. Oppositely, CpG3 induces in MDM an excessive and unregulated inflammatory response unable to contain MTB infection.

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CpG oligodeoxynucleotides promote phospholipase D dependent phagolysosome maturation and intracellular mycobacterial killing in M. tuberculosis infected type II alveolar epithelial cells

Cited by 7 publications

References 18 publications

Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

Mycobacterium abscessus Glycopeptidolipid Prevents Respiratory Epithelial TLR2 Signaling as Measured by HβD2 Gene Expression and IL-8 Release

Use of CpG Oligonucleotides as Mucosal Adjuvants

A New CpG ODN Induces a Fine-Tuning of Innate Response Resulting in Mycobacterium tuberculosis Containment

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