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, 7 (2), e31976

Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated With the Airway Microbiota

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Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated With the Airway Microbiota

Jeppe Madura Larsen et al. PLoS One.

Abstract

Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota.

Conflict of interest statement

Competing Interests: The study was funded by a independent research grant to SB from the Lundbeck Foundation. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The authors have no other competing interests to declare.

Figures

Figure 1
Figure 1. Maturation of dendritic cells stimulated with pathogenic and commensal airway bacteria.
CD83, CD40 and CD86 expression by DCs in response to 24 h stimulation with medium, LPS, Haemophilus influenzae B (H. inf. B), non-typeable Haemophilus influenzae (H. inf. NT), Moraxella catarrhalis (M. cat.), Prevotella melaninogenica (P. mel.), Prevotella nanceiensis (P. nan.), Prevotella salivae (P. sal.), Veillonella dispar (V. disp.), Actinomyces graevenitzii (A. grae.) or Actinomyces oris (A. oris.). DCs were gated on viable cells. The geometric mean fluorescence intensity of the indicated marker is given on each chart. Data represents the response from one donor out of two.
Figure 2
Figure 2. Cytokine production by dendritic cells stimulated with pathogenic and commensal airway bacteria.
IL-23, IL-12p70 and IL-10 cytokine production measured in DC culture supernatants following 24 h stimulation with medium, LPS, Haemophilus influenzae B (H. inf. B), non-typeable Haemophilus influenzae (H. inf. NT), Moraxella catarrhalis (M. cat.), Prevotella melaninogenica (P. mel.), Prevotella nanceiensis (P. nan.), Prevotella salivae (P. sal.), Veillonella dispar (V. disp.), Actinomyces graevenitzii (A. grae.) or Actinomyces oris (A. oris.). Labels within each group represent different donors (n = 3–9). Cytokine production measurements were normalized to account for donor-specific variation. *p<0.05, **p<0.01, ***p<0.001.
Figure 3
Figure 3. Principal component analysis of dendritic cell cytokine profiles in response to pathogenic and commensal airway bacteria.
Principal component analysis reveals clustering of DC responses to airway bacteria. Three significantly different groups are distinguished by the production of IL-23, IL-12p70 and IL-10 cytokines. I: Pathogenic Gram-negative Haemophilus influenzae B (H. inf. B), non-typeable Haemophilus influenzae (H. inf. NT) and Moraxella catarrhalis (M. cat.); II: Commensal Gram-negative Prevotella melaninogenica (P. mel.), Prevotella nanceiensis (P. nan.), Prevotella salivae (P. sal.) and Veillonella dispar (V. disp.); III: Commensal Gram-positive Actinomyces graevenitzii (A. grae.) and Actinomyces oris (A. oris.). Responses to each bacterium were based on 3–6 different donors. Shaded areas represent the 67% confidence area within the three bacteria groups.
Figure 4
Figure 4. Modulation of Haemophilus-induced cytokine production in dendritic cells by Prevotella species.
IL-23, IL-12p70 and IL-10 cytokine production measured in DC culture supernatants 24 h following stimulation with non-typeable Haemophilus influenzae (H. inf. NT) in combination with Prevotella melaninogenica (P. mel.), Prevotella nanceiensis (P. nan.) or Prevotella salivae (P. sal.). The effect of Prevotella species on Haemophilus-induced cytokine production was calculated relative to Haemophilus stimulation alone for each donor. The numbers identify individual donors (n = 3–5). *p<0.05, **p<0.01.

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