Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Meer, Anne Jan van der; Achouiti, Achmed; Ende, Arie van der; Soussan, Aïcha Ait; Florquin, Sandrine; Vos, Anneke S. de; Poll, Tom van der

doi:10.2119/molmed.2015.00242

Cited by 13 publications

(11 citation statements)

References 47 publications

(55 reference statements)

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“…However, this did not affect bacterial clearance (Fig 3D) or lung injury (Fig 3E) as both were reduced significantly 48 h post-infection in both genotypes. Previous work has shown that TLR9 -/- mice have reduced TNF-α in the bronchoalveolar lavage fluid (BALF) post-MRSA [19]. We detected lower amounts of TNF-α, IL-6, IL-1β and IL-10 in the BALF of MRSA-infected TLR9 -/- mice (Fig 3F).…”

Section: Resultssupporting

confidence: 51%

“…Currently, there are conflicting results regarding the role of TLR9 in single MRSA infection [18, 19]. To understand if TLR9 -/- mice were susceptible to a single MRSA infection, we monitored mice for 7 days post-infection.…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports focused on the role of TLR9 in single MRSA infection have shown conflicting results. TLR9 -/- mice were reported to have decreased MRSA clearance despite showing a lower amount of TNF-α [19]. In contrast, MRSA was shown to induce a type I interferon response dependent on TLR9, and TLR9 -/- mice were reported to have lower TNF-α and improved bacterial clearance [18].…”

Section: Discussionmentioning

confidence: 99%

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Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

et al. 2019

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Bacterial lung infections, particularly with methicillin-resistant Staphylococcus aureus (MRSA), increase mortality following influenza infection, but the mechanisms remain unclear. Here we show that expression of TLR9, a microbial DNA sensor, is increased in murine lung macrophages, dendritic cells, CD8+ T cells and epithelial cells post-influenza infection. TLR9-/- mice did not show differences in handling influenza nor MRSA infection alone. However, TLR9-/- mice have improved survival and bacterial clearance in the lung post-influenza and MRSA dual infection, with no difference in viral load during dual infection. We demonstrate that TLR9 is upregulated on macrophages even when they are not themselves infected, suggesting that TLR9 upregulation is related to soluble mediators. We rule out a role for elevations in interferon-γ (IFNγ) in mediating the beneficial MRSA clearance in TLR9-/- mice. While macrophages from WT and TLR9-/- mice show similar phagocytosis and bacterial killing to MRSA alone, following influenza infection, there is a marked upregulation of scavenger receptor A and MRSA phagocytosis as well as inducible nitric oxide synthase (Inos) and improved bacterial killing that is specific to TLR9-deficient cells. Bone marrow transplant chimera experiments and in vitro experiments using TLR9 antagonists suggest TLR9 expression on non-hematopoietic cells, rather than the macrophages themselves, is important for regulating myeloid cell function. Interestingly, improved bacterial clearance post-dual infection was restricted to MRSA, as there was no difference in the clearance of Streptococcus pneumoniae. Taken together these data show a surprising inhibitory role for TLR9 signaling in mediating clearance of MRSA that manifests following influenza infection.

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Section: Resultssupporting

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

et al. 2019

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“…Data obtained in other infection models indicate that TLR9 can be activated by bacterial and host DNA released into the airways during pneumonia (van der Meer et al. 2016 ), as well as by intracellular bacteria and DNA of mitochondrial origin released to the cytosol upon infection (Zhang et al. 2010 ; Arpaia et al.…”

Section: Contribution Of Host Signalling In Defence Against mentioning

confidence: 99%

Klebsiella pneumoniaeinfection biology: living to counteract host defences

Bengoechea

Sá‐Pessoa

2018

FEMS Microbiology Reviews

349

300

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Klebsiella species cause a wide range of diseases including pneumonia, urinary tract infections (UTIs), bloodstream infections and sepsis. These infections are particularly a problem among neonates, elderly and immunocompromised individuals. Klebsiella is also responsible for a significant number of community-acquired infections. A defining feature of these infections is their morbidity and mortality, and the Klebsiella strains associated with them are considered hypervirulent. The increasing isolation of multidrug-resistant strains has significantly narrowed, or in some settings completely removed, the therapeutic options for the treatment of Klebsiella infections. Not surprisingly, this pathogen has then been singled out as an ‘urgent threat to human health’ by several organisations. This review summarises the tremendous progress that has been made to uncover the sophisticated immune evasion strategies of K. pneumoniae. The co-evolution of Klebsiella in response to the challenge of an activated immune has made Klebsiella a formidable pathogen exploiting stealth strategies and actively suppressing innate immune defences to overcome host responses to survive in the tissues. A better understanding of Klebsiella immune evasion strategies in the context of the host–pathogen interactions is pivotal to develop new therapeutics, which can be based on antagonising the anti-immune strategies of this pathogen.

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“…It was reported that TLR9 contributes to improved protective innate immunity against Gram-negative bacteria pneumonia by rapid accumulation of dendritic cells in the lung [9]. TLR9 also leads to bacterial clearance against Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) infection [10,11].…”

Section: Introductionmentioning

confidence: 99%

Anti-Bacterial Effect of CpG-DNA Involves Enhancement of the Complement Systems

Kim

Park

Kim

et al. 2019

IJMS

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CpG-DNA activates the host immune system to resist bacterial infections. In this study, we examined the protective effect of CpG-DNA in mice against Escherichia coli (E. coli) K1 infection. Administration of CpG-DNA increased the survival of mice after E. coli K1 infection, which reduces the numbers of bacteria in the organs. Pre-injection of mice with CpG-DNA before E. coli K1 infection increased the levels of the complement C3 but not C3a and C3b. The survival of the mice after E. coli K1 infection was significantly decreased when the mice were pre-injected with the cobra venom factor (CVF) removing the complement compared to the non-CVF-treated mice group. It suggests that the complement has protective roles against E. coli K1 infection. In addition, the survival of complement-depleted mice was increased by CpG-DNA pre-administration before E. coli K1 infection. Therefore, we suggest that CpG-DNA enhances the anti-bacterial activity of the immune system by augmenting the levels of complement systems after E. coli K1 infection and triggering other factors as well. Further studies are required to investigate the functional roles of the CpG-DNA-induced complement regulation and other factors against urgent bacterial infection.

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Toll-Like Receptor 9 Enhances Bacterial Clearance and Limits Lung Consolidation in Murine Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus

Cited by 13 publications

References 47 publications

Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

Klebsiella pneumoniaeinfection biology: living to counteract host defences

Anti-Bacterial Effect of CpG-DNA Involves Enhancement of the Complement Systems

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