Bordetella pertussis filamentous hemagglutinin itself does not trigger anti-inflammatory interleukin-10 production by human dendritic cells

Romero, Rodrigo Villarino; Hasan, Shakir; Faé, Kellen C.; Holubová, Jana; Geurtsen, Jeroen; Schwarzer, Martin; Wiertsema, Selma P.; Osička, Radim; Poolman, Jan; Šebo, Peter

doi:10.1016/j.ijmm.2015.11.003

Cited by 13 publications

(10 citation statements)

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“…pertussis whole genome sequences [27] revealed no polymorphism for these genes in strains carrying the ptxP1 , ptxP2 or ptxP3 alleles.These findings suggest that differential gene expression or post-translational modifications may explain the observed differences or that other TLR2 ligands are involved. For example, FHA has been proposed as a TLR2 ligand although this remains debatable [38, 39]. …”

Section: Discussionmentioning

confidence: 99%

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

et al. 2017

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Vaccines against pertussis have been available for more than 60 years. Nonetheless, this highly contagious disease is reemerging even in countries with high vaccination coverage. Genetic changes of Bordetella pertussis over time have been suggested to contribute to the resurgence of pertussis, as these changes may favor escape from vaccine-induced immunity. Nonetheless, studies on the effects of these bacterial changes on the immune response are limited. Here, we characterize innate immune recognition and activation by a collection of genetically diverse B. pertussis strains isolated from Dutch pertussis patients before and after the introduction of the pertussis vaccines. For this purpose, we used HEK-Blue cells transfected with human pattern recognition receptors TLR2, TLR4, NOD2 and NOD1 as a high throughput system for screening innate immune recognition of more than 90 bacterial strains. Physiologically relevant human monocyte derived dendritic cells (moDC), purified from peripheral blood of healthy donors were also used. Findings indicate that, in addition to inducing TLR2 and TLR4 signaling, all B. pertussis strains activate the NOD-like receptor NOD2 but not NOD1. Furthermore, we observed a significant increase in TLR2 and NOD2, but not TLR4, activation by strains circulating after the introduction of pertussis vaccines. When using moDC, we observed that the recently circulating strains induced increased activation of these cells with a dominant IL-10 production. In addition, we observed an increased expression of surface markers including the regulatory molecule PD-L1. Expression of PD-L1 was decreased upon blocking TLR2. These in vitro findings suggest that emerging B. pertussis strains have evolved to dampen the vaccine-induced inflammatory response, which would benefit survival and transmission of this pathogen. Understanding how this disease has resurged in a highly vaccinated population is crucial for the design of improved vaccines against pertussis.

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Section: Discussionmentioning

confidence: 99%

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

et al. 2017

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“…FHA-induced IL-10 also dampens IL-12 production by DCs and leads to downregulation of protective Th17 and Th1 responses (79). However, it must be noted that more recent research has cast a question mark over the immunoregulatory role of FHA (106). The authors state that the upregulation of IL-10 may be caused by endotoxin contamination or co-purification of bacterial lipoproteins, which may contribute to FHA's cytokine inducing activity (106,107).…”

Section: Il-10mentioning

confidence: 99%

“…However, it must be noted that more recent research has cast a question mark over the immunoregulatory role of FHA (106). The authors state that the upregulation of IL-10 may be caused by endotoxin contamination or co-purification of bacterial lipoproteins, which may contribute to FHA's cytokine inducing activity (106,107). Adenylate cyclase toxin (ACT) of B. pertussis also drives IL-10 production by APCs such as DCs and macrophages (77,108), which then further induces IL-10-secreting Treg cells (109).…”

Section: Il-10mentioning

confidence: 99%

Target the Host, Kill the Bug; Targeting Host Respiratory Immunosuppressive Responses as a Novel Strategy to Improve Bacterial Clearance During Lung Infection

Kelly

McLoughlin

2020

Front. Immunol.

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The lung is under constant pressure to protect the body from invading bacteria. An effective inflammatory immune response must be tightly orchestrated to ensure complete clearance of any invading bacteria, while simultaneously ensuring that inflammation is kept under strict control to preserve lung viability. Chronic bacterial lung infections are seen as a major threat to human life with the treatment of these infections becoming more arduous as the prevalence of antibiotic resistance becomes increasingly commonplace. In order to survive within the lung bacteria target the host immune system to prevent eradication. Many bacteria directly target inflammatory cells and cytokines to impair inflammatory responses. However, bacteria also have the capacity to take advantage of and strongly promote anti-inflammatory immune responses in the host lung to inhibit local pro-inflammatory responses that are critical to bacterial elimination. Host cells such as T regulatory cells and myeloid-derived suppressor cells are often enhanced in number and activity during chronic pulmonary infection. By increasing suppressive cell populations and cytokines, bacteria promote a permissive environment suitable for their prolonged survival. This review will explore the anti-inflammatory aspects of the lung immune system that are targeted by bacteria and how bacterial-induced immunosuppression could be inhibited through the use of host-directed therapies to improve treatment options for chronic lung infections.

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“…As this domain is not included in the 80 kDa N-terminal fragment of Fha, this TLR2-stimulatory activity may be responsible for the IL-10 production induced by full-length Fha. However, Sebo’s group reported that the cytokine-inducing and TLR2-stimulating activities of Fha preparations are because of contaminating endotoxin [23 ▪ ], calling the findings on Fha immunostimulatory properties into doubt. Studying the closely related pathogen Bordetella bronchiseptica in a mouse model of respiratory infection, Cotter’s group found that the FhaB preprotein appears to play a role in bacterial persistence in the airways [24 ▪ ].…”

Section: Role and Activity Of B Pertussis Virulence Factorsmentioning

confidence: 99%

Bordetella pertussis

Carbonetti

2016

Current Opinion in Infectious Diseases

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Purpose of review The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines. Recent findings Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions. Summary Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention.

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Bordetella pertussis filamentous hemagglutinin itself does not trigger anti-inflammatory interleukin-10 production by human dendritic cells

Cited by 13 publications

References 53 publications

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

Emerging Bordetella pertussis Strains Induce Enhanced Signaling of Human Pattern Recognition Receptors TLR2, NOD2 and Secretion of IL-10 by Dendritic Cells

Target the Host, Kill the Bug; Targeting Host Respiratory Immunosuppressive Responses as a Novel Strategy to Improve Bacterial Clearance During Lung Infection

Bordetella pertussis

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