Neutrophils Exert a Suppressive Effect on Th1 Responses to Intracellular Pathogen Brucella abortus

Barquero-Calvo, Elías; Martirosyan, Anna; Ordoñez-Rueda, Diana; Arce‐Gorvel, Vilma; Alfaro-Alarcón, Alejandro; Lépidi, Hubert; Malissen, Bernard; Gorvel, Jean‐Pierre; Moreno, Edgardo

doi:10.1371/journal.ppat.1003167

Cited by 36 publications

(74 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MoDC-derived IL-4 was low or undetectable, suggesting that this cytokine did not play a role in driving Th2 polarization in our model. In some circumstances, PMN are known to favor Th2 polarization in vitro (57); moreover, in vivo, in a bacterial infection model, neutrophildeficient mice exhibit enhanced Th1 responses and diminished Th2 responses (63). Proteases are candidate NET constituents that might be involved in inducing Th2 responses, as already described for several allergen serine proteases such as dust mite (61).…”

Section: Discussionmentioning

confidence: 98%

Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

Barrientos

Bignon

Gueguen

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Polymorphonuclear neutrophils (PMN) play a central role in inflammation and participate in its control, notably by modulating dendritic cell (DC) functions via soluble mediators or cell–cell contacts. Neutrophil extracellular traps (NETs) released by PMN could play a role in this context. To evaluate NET effects on DC maturation, we developed a model based on monocyte-derived DC (moDC) and calibrated NETs isolated from fresh human PMN. We found that isolated NETs alone had no discernable effect on moDC. In contrast, they downregulated LPS-induced moDC maturation, as shown by decreased surface expression of HLA-DR, CD80, CD83, and CD86, and by downregulated cytokine production (TNF-α, IL-6, IL-12, IL-23), with no increase in the expression of tolerogenic DC genes. Moreover, the presence of NETs during moDC maturation diminished the capacity of these moDC to induce T lymphocyte proliferation in both autologous and allogeneic conditions, and modulated CD4+ T lymphocyte polarization by promoting the production of Th2 cytokines (IL-5 and IL-13) and reducing that of Th1 and Th17 cytokines (IFN-γ and IL-17). Interestingly, the expression and activities of the lymphoid chemokine receptors CCR7 and CXCR4 on moDC were not altered when moDC matured in the presence of NETs. Together, these findings reveal a new role for NETs in adaptive immune responses, modulating some moDC functions and thereby participating in the control of inflammation.

show abstract

Section: Discussionmentioning

confidence: 98%

Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

Barrientos

Bignon

Gueguen

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In their absence there was more IFN-γ produced and less of the Th2 cytokine IL-4. Moreover, there was a greater infiltration of macrophages and dendritic cells into the spleens of mice without neutrophils (40). Similarly surprising was the observation that the bacteria in a primary infection were controlled in the absence of antibodies as well as in their presence (36).…”

Section: Insights Into Anti-brucella Immune Responsesmentioning

confidence: 89%

The quest for a true One Health perspective of brucellosis

Godfroid¹,

DeBolle²,

Roop³

et al. 2014

Rev. Sci. Tech. OIE

View full text Add to dashboard Cite

SummaryOne Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis. Likewise, management of brucellosis at the wildlife-livestock interface in wildlife conservation areas is in essence different from mitigating transmission of a given Brucella species within its preferential host species, which in turn is different from mitigating the spillover of a given Brucella species to non-preferential host species, humans included. Brucellosis economic models often oversimplify and/or wrongly assess transmission between reservoir hosts and spillover hosts. Moreover, they may not properly value non-market outcomes, such as avoidance of human disease, consumer confidence and conservation biology issues. As a result, uncertainty is such that the economic predictions of these models can be questionable. Therefore, understanding the infection biology of Brucella species is a prerequisite. This paper reviews and highlights important features of the infection biology of Brucella species and the changing epidemiology of brucellosis that need to be integrated into a true One Health perspective of brucellosis.

show abstract

“…In an Ehrlichia muris infection model (70), IFN-g was shown to control infection by directly promoting the differentiation of myeloid cells into monocytes. In the absence of IFN-g signaling, E. muris infection only promotes the expansion of neutrophils, which do not play a protective role during Brucella infection (71) and are generally associated with massive tissue damage, particularly in the lungs (reviewed in Ref. 72).…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Mambres

Machelart

Potemberg

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis. Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35−/− mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35– and IL-17A–dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4+ and CD8+ α/β+ T cells are sufficient to mount a protective immune response and that an IL-17A–mediated response can compensate for the partial deficiency of an IFN-γ–mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ–and IL-17RA–mediated responses in the control of mucosal infection by Brucella.

show abstract

Neutrophils Exert a Suppressive Effect on Th1 Responses to Intracellular Pathogen Brucella abortus

Cited by 36 publications

References 54 publications

Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells

The quest for a true One Health perspective of brucellosis

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Contact Info

Product

Resources

About