Neonates colonized with pathogenic bacteria in the airways have a low‐grade systemic inflammation

Fink, Nadia R.; Chawes, Bo; Thorsen, Jonathan; Stokholm, Jakob; Krogfelt, Karen A.; Schjørring, Susanne; Kragh, Marie; Bønnelykke, Klaus; Brix, Susanne; Bisgaard, Hans

doi:10.1111/all.13461

Cited by 15 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the fact that respiratory IAV infection went unchanged, we explored whether respiratory carriage with B. bronchiseptica affected responses against a systemic bacterial infection. Of note, only recently asymptomatic colonization with Moraxella catharralis , Haemophilus influenzae, and/or Streptococcus pneumoniae in the hypopharynx, was shown to be associated with low-grade systemic inflammation in new-born children [ 18 ]. Surprisingly, we found B. bronchiseptica carriage to display a significant benefit for the host, regarding the control of systemic L. monocytogenes infection.…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, there is an increasing awareness of immune regulatory effects across compartments to remote sites, which to date are most appreciated for the gut microbiome [ 13 , 15 , 16 ]. Nevertheless, there is also evidence for inflammatory processes in the respiratory tract to influence systemic immunity [ 13 , 17 , 18 , 19 ]. While we are only beginning to understand these multi-faceted interactions, the underlying mechanisms to date remain mostly elusive.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Jeron

Boehme

Volckmar

et al. 2018

IJMS

View full text Add to dashboard Cite

The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica as the underlying model to comprehensively address effects on subsequent immune responses. Carriage was associated with the stimulation of Bordetella-specific CD4+, CD8+, and CD4+CD25+Foxp3+ T cell responses, and broad transcriptional activation was observed in CD4+CD25+ T cells. Importantly, transfer of leukocytes from carriers to acutely B. bronchiseptica infected mice, resulted in a significantly increased bacterial burden in the recipient’s upper respiratory tract. In contrast, we found that respiratory B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. Adaptive responses to vaccination and influenza A virus infection, were unaffected by B. bronchiseptica carriage. These data showed that there were significant immune modulatory processes triggered by B. bronchiseptica carriage, that differentially affect subsequent immune responses. Therefore, our results demonstrated the complexity of immune regulation induced by respiratory bacterial carriage, which can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Jeron

Boehme

Volckmar

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…St. aureus was associated with a TH17 profile and elevated IL-17; of note, there was no signal with S. pneumoniae colonization. Subsequent work on outcomes in colonized children has shown that they have increased troublesome non-specific respiratory symptoms (74), an increased risk of bronchiolitis and pneumonia (75), and interestingly, have low grade systemic inflammation as shown by an elevated hs-CRP (76). Furthermore, children given a diagnosis of asthma at age 7 years were shown to have increased levels of IL-5 and IL-13 when their peripheral blood mononuclear cells harvested at age 6 months were stimulated with H. influenzae, M. catarrhalis , and S. pneumoniae , and also increased IL-17 and IL-10 when stimulated by H. influenzae and M. catarrhalis , but not S. pneumoniae (72, 73).…”

Section: The First Steps: Episodic Viral Wheezementioning

confidence: 99%

Cytokines and Chemokines as Biomarkers of Future Asthma

Bush

2019

Front. Pediatr.

View full text Add to dashboard Cite

Antenatal and preschool factors are key in determining the progression to pre-school wheeze and eosinophilic school age asthma. The conventional view of eosinophilic asthma is that airway inflammation is the fundamental underlying abnormality, and airway inflammation and hyper-responsiveness are secondary; in fact, these three are parallel processes. Very early structural changes, independent of inflammation and infection, are associated with early airway hyper-responsiveness and later adverse respiratory outcomes. There is a bidirectional relationship between structural airway wall changes and airway inflammation, with airway contraction per se leading to the release of growth factors, and inflammatory pathways promoting airway remodeling. Early viral infection (and increasingly being appreciated, bacterial infection) is important in wheeze outcomes. There is evidence of abnormal immune function including cytokine release before the onset of viral infections. However, viral infections may also have prolonged effects on the host immune system, and the evidence for beneficial and adverse effects of viral infection is conflicting. In older children and adults, asthmatic epithelial cells show impaired interferon responses to viral infection, but only in the presence of uncontrolled type 2 inflammation, implying these are secondary phenomena. There are also compelling data relating the innate immune system to later asthma and atopy, and animal studies suggest that the effects of a high endotoxin, microbiologically diverse environment may be modulated via the epithelial alarmin IL-33. Whereas, previously only viral infection was thought to be important, early bacterial colonization of the upper airway is coming to the fore, associated with a mixed pattern of TH1/TH2/TH17 cytokine secretion, and adverse long term outcomes. Bacterial colonization is probably a marker of a subtle immune deficiency, rather than directly causal. The airway and gut microbiome critically impacts the development of Type 2 inflammatory responses. However, Type 2 inflammatory cytokines, which are critical both to progression from pre-school wheeze to eosinophilic asthma, and sustaining the eosinophilic asthmatic state, are not implicated in the very early development of the disease. Taken together, the evidence is that the earliest cytokine and chemokine signals will come from the study of bronchial epithelial cell function and their interactions with viruses and the microbiome.

show abstract

“…Additionally, the immune system might also affect the risk of bacterial airway colonization with microorganisms 26 . Airway bacterial carriage in early life has been associated with a low‐grade systemic inflammation at age 6 months, including C‐reactive protein and interleukin‐6, which could also affect the risk of wheezing or asthma 27 . Bacterial carriage might influence the risk of lower respiratory tract infections and vice versa 21 .…”

Section: Discussionmentioning

confidence: 99%

Airway bacterial carriage and childhood respiratory health: A population‐based prospective cohort study

Meel

Jaddoe

Looman

et al. 2020

Pediatric Allergy Immunology

View full text Add to dashboard Cite

show abstract

Neonates colonized with pathogenic bacteria in the airways have a low‐grade systemic inflammation

Abstract: The composition of the upper airway microbiome in early life may cause systemic low-grade inflammation.

Cited by 15 publications

References 35 publications

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice

Cytokines and Chemokines as Biomarkers of Future Asthma

Airway bacterial carriage and childhood respiratory health: A population‐based prospective cohort study

Contact Info

Product

Resources

About