HRV16 Impairs Macrophages Cytokine Response to a Secondary Bacterial Trigger

Jubrail, Jamil; Africano-Gomez, Kshanti; Herit, Floriane; Baturcam, Engin; Mayer, Gaëll; Cunoosamy, Danen; Kurian, Nisha; Niedergang, Florence

doi:10.3389/fimmu.2018.02908

Cited by 9 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that this was not the case, further emphasising that HRV16 specifically affected the internalisation step. These results are important in the context of COPD where HRV is frequently isolated [20] and, together with other defective functions like cell activation [13,[22][23][24], could be one of the explanations as to why patients show bacterial outgrowths post-HRV infection [13,19]. Phagocytosis is strictly dependent on actin polymerisation (for review, Refs.…”

Section: Discussionmentioning

confidence: 95%

“…However, mounting evidence shows that HRV can infect the lower respiratory tract in patients with chronic inflammatory diseases including chronic obstructive pulmonary disease (COPD) driving disease exacerbations [17][18][19][20]. How HRV disrupts macrophage/monocyte functions remains unknown, but HRV was reported to induce a defective secondary response in macrophages [13,[22][23][24]. How HRV disrupts macrophage/monocyte functions remains unknown, but HRV was reported to induce a defective secondary response in macrophages [13,[22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, in subjects experimentally infected with RV16, RV was ingested by recruited CD68-positive and CD11b-positive macrophages in asthmatic humans, providing direct evidence that tissue macrophages in the lower airways contribute to anti-RV responses in vivo [21]. How HRV disrupts macrophage/monocyte functions remains unknown, but HRV was reported to induce a defective secondary response in macrophages [13,[22][23][24].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

et al. 2019

Self Cite

View full text Add to dashboard Cite

Human rhinovirus is a causative agent of severe exacerbations of chronic obstructive pulmonary disease (COPD). COPD is characterised by an increased number of alveolar macrophages with diminished phagocytic functions, but how rhinovirus infection affects macrophage function is still unknown. Here, we describe that human rhinovirus 16 impairs bacterial uptake and receptormediated phagocytosis in macrophages. The stalled phagocytic cups contain accumulated F-actin. Interestingly, we find that human rhinovirus 16 downregulates the expression of Arpin, a negative regulator of the Arp2/3 complex. Importantly, re-expression of the protein rescues defective internalisation in human rhinovirus 16-treated cells, demonstrating that Arpin is a key factor targeted to impair phagocytosis. We further show that Arpin is required for efficient uptake of multiple targets, for F-actin cup formation and for successful phagosome completion in macrophages. Interestingly, Arpin is recruited to sites of membrane extension and phagosome closure. Thus, we identify Arpin as a central actin regulator during phagocytosis that it is targeted by human rhinovirus 16, allowing the virus to perturb bacterial internalisation and phagocytosis in macrophages.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In COPD, rhinovirus specifically has been shown to impair bacterial phagocytosis by macrophages [ 34 ]. Others, using in vitro experiments, have shown alveolar macrophages are less able to mount an immune response to bacteria following HRV infection [ 35 , 36 ]. Viruses clearly play a role in the airway, the most significant of which may be their interaction with immune defense and bacteria.…”

Section: Discussionmentioning

confidence: 99%

Early respiratory viral infections in infants with cystic fibrosis

Deschamp

Hatch

Slaven

et al. 2019

Journal of Cystic Fibrosis

View full text Add to dashboard Cite

a b s t r a c tBackground: Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods: Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results: Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0-10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions: Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF.

show abstract

“…Unlike the here described RV-induced priming effect, infection of MΦ with human rhinovirus instead of RV has been reported to impair the cytokine response to LPS ( 50 ). Thus, the type of virus seems to be crucial for the outcome of a secondary bacterial stimulation and no predictions can be made.…”

Section: Discussionmentioning

confidence: 71%

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

et al. 2021

View full text Add to dashboard Cite

Macrophages (MΦ) are known to exhibit distinct responses to viral and bacterial infection, but how they react when exposed to the pathogens in succession is less well understood. Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by an LPS-induced challenge on cytokine production, signal transduction and metabolic pathways in human GM (M1-like)- and M (M2-like)-MΦ. We found that infection of both subsets with RV resulted in a low TNF-α and a high interferon (IFN, type I and type III) release whereby M-MΦ produced far more IFNs than GM-MΦ. Thus, TNF-α production in contrast to IFN production is not a dominant feature of RV infection in these cells. Upon addition of LPS to RV-infected MΦ compared to the addition of LPS to the uninfected cells the TNF-α response only slightly increased, whereas the IFN-response of both subtypes was greatly enhanced. The subset specific cytokine expression pattern remained unchanged under these assay conditions. The priming effect of RV was also observed when replacing RV by IFN-β one putative priming stimulus induced by RV. Small amounts of IFN-β were sufficient for phosphorylation of Stat1 and to induce IFN-production in response to LPS. Analysis of signal transduction pathways activated by successive exposure of MΦ to RV and LPS revealed an increased phosphorylation of NFκB (M-MΦ), but different to uninfected MΦ a reduced phosphorylation of ERK1/2 (both subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show that RV infection and exogenously added IFN-β can prime MΦ to produce high amounts of IFNs in response to LPS and that changes in glycolysis and signal transduction are associated with the priming effect. These findings will help to understand to what extent MΦ defense to viral infection is modulated by a following exposure to a bacterial infection.

show abstract

HRV16 Impairs Macrophages Cytokine Response to a Secondary Bacterial Trigger

Cited by 9 publications

References 41 publications

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus

Early respiratory viral infections in infants with cystic fibrosis

The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages

Contact Info

Product

Resources

About