GM-CSF treatment prevents respiratory syncytial virus–induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation

Naessens, Thomas; Schepens, Bert; Smet, Muriel; Pollard, Charlotte; Hoecke, Lien Van; Beuckelaer, Alain De; Willart, Monique; Lambrecht, Bart; Koker, Stefaan De; Saelens, Xavier; Grooten, Johan

doi:10.1016/j.jaci.2015.09.031

Cited by 17 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In concert with these findings, RSV lung titers were not reduced in GM-CSF-treated mice compared to PBS-treated control animals. The findings reported here in infant mice, contradict previous studies in adult mice demonstrating that GM-CSF increases alveolar macrophage activation and reduces RSV lung titers in adult mice [24, 27]. …”

Section: Discussioncontrasting

confidence: 95%

“…Pulmonary dendritic cells (DCs) further contribute to the anti-viral cytokine milieu in the lung during viral infection and are essential for antigen presentation and initiation of adaptive immunity. However, efficient anti-viral cytokine production and engagement of the adaptive immune response depends largely on AM and DC maturation, suggesting that the Th2-dominant infant lung environment limits maturation and activation of innate immune cells and their anti-viral activity [25–27]. Thus, local exposure to pro-inflammatory cytokines in the lung is critical for proper innate cell maturation and disease resolution.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection

et al. 2017

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life. Severe RSV disease during infancy has also been linked to the later development of allergic asthma, yet there remains no licensed RSV vaccine or treatment. Pre-clinical and clinical studies have shown that disease severity and development of allergic asthma are associated with differences in cytokine production. As a result, stimulation of the innate host immune response with immune potentiators is gaining attention for their prospective application in populations with limited immune responses to antigenic stimuli or against pathogens for which vaccines do not exist. Specifically, macrophage-activating cytokines such as interferon gamma (IFNγ) and granulocyte colony-stimulating factor (GM-CSF) are commercially available immune potentiators used to prevent infections in patients with chronic granulomatous disease and febrile neutropenia, respectively. Moreover, an increasing number of reports describe the protective function of IFNγ and GM-CSF as vaccine adjuvants. Although a positive correlation between cytokine production and age has previously been reported, little is known about age-dependent cytokine metabolism or immune activating responses in infant compared to adult lungs. Here we use a non-compartmental pharmacokinetic model in naïve and RSV-infected infant and adult BALB/c mice to determine the effect of age on IFNγ and GM-CSF elimination and innate cell activation following intranasal delivery.

show abstract

Section: Discussioncontrasting

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Moreover, the activation of AMs with IFN-γ promotes the clearing of the viral infection [ 143 ]. Additionally, the expansion of the AM subset in mice recently recovered from allergically induced eosinophilia leads to a reduced hRSV immunopathology [ 144 ], supporting the notion that AMs play a protective role in hRSV infection.…”

Section: Differential Regulation Of the Innate Immune Response By mentioning

confidence: 89%

Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

Andrade

Pacheco

Gálvez

et al. 2020

Viruses

View full text Add to dashboard Cite

The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.

show abstract

“…Indeed, maturation of resident AMs has been reported to be deficient in the context of allergic inflammation, and this was attributable to a relative deficiency of GM-CSF; intrapulmonary administration of GM-CSF was found to promote AM maturation and enhance their ability to protect against viral exacerbations of asthma in a mouse model [72•]. Such an approach might have the additional benefit of enhancing proliferation of AMs [73].…”

Section: Emerging Therapiesmentioning

confidence: 99%

Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Draijer

Peters‐Golden

2017

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Purpose of Review The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation. Recent Findings Immediately after allergen exposure, monocytes are rapidly recruited from the bloodstream and serve to promote acute inflammation. By contrast, resident alveolar macrophages play a predominantly suppressive role in an effort to restore homeostasis. As inflammation becomes established after repeated exposures, alveolar macrophages can polarize across a continuum of activation phenotypes, losing their suppressive functions and gaining pathogenic functions. Summary Future research should focus on the diverse roles of monocytes/macrophages during various types and phases of allergic inflammation. These properties could lead us to new therapeutic opportunities.

show abstract

GM-CSF treatment prevents respiratory syncytial virus–induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation

Cited by 17 publications

References 35 publications

Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection

Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection

Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Contact Info

Product

Resources

About