Monocyte-mediated defense against bacteria, fungi, and parasites

Lauvau, Grégoire; Loke, P’ng; Hohl, Tobias M.

doi:10.1016/j.smim.2016.03.014

Cited by 59 publications

(40 citation statements)

References 154 publications

(195 reference statements)

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“…DCs present foreign antigens on their surface, thus activating cytotoxic T cells. Macrophages on the other hand respond following activation with a ROS burst, thereby killing pathogens that are later engulfed by macrophage phagocytosis [1–4]. Also monocytes respond with ROS production following activation, and the same is true for neutrophilic granulocytes (as shown in Figs 2 and 7).…”

Section: Discussionmentioning

confidence: 99%

“…Monocytes move via the bloodstream to peripheral tissues where they differentiate, depending on the local growth factors, cytokines, and microbial molecules, into macrophages or myeloid dendritic cells (DCs) [2]. Monocytes are also recruited to sites of infection and mediate anti-microbial activity against viruses, bacteria, fungi and protozoa [3,4]. As first line defence, monocytes and macrophages can phagocytose pathogens and foreign particles, release cytokines and generate reactive oxygen species (ROS) in a “respiratory burst” [5–7].…”

Section: Introductionmentioning

confidence: 99%

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Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans

Ponath

Kaina

2017

PLoS ONE

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Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to the pathogenesis of inflammatory diseases. Therefore, a mechanism maintaining a balance in the monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired in DNA repair, rendering them vulnerable to genotoxic stress while monocyte-derived macrophages are DNA repair competent and genotoxic stress-resistant. Based on these findings, we hypothesized that monocytes can be selectively killed by reactive oxygen species (ROS) produced by activated macrophages. We also wished to know whether monocytes and macrophages are protected against their own ROS produced following activation. To this end, we studied the effect of the ROS burst on DNA integrity, cell death and differentiation potential of monocytes. We show that monocytes, but not macrophages, stimulated for ROS production by phorbol-12-myristate-13-acetate (PMA) undergo apoptosis, despite similar levels of initial DNA damage. Following co-cultivation with ROS producing macrophages, monocytes displayed oxidative DNA damage, accumulating DNA single-strand breaks and a high incidence of apoptosis, reducing their ability to give rise to new macrophages. Killing of monocytes by activated macrophages, termed killing in trans, was abolished by ROS scavenging and was also observed in monocytes co-cultivated with ROS producing activated granulocytes. The data revealed that monocytes, which are impaired in the repair of oxidised DNA lesions, are vulnerable to their own ROS and ROS produced by macrophages and granulocytes and support the hypothesis that this is a mechanism regulating the amount of monocytes and macrophages in a ROS-enriched inflammatory environment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans

Ponath

Kaina

2017

PLoS ONE

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“…MDC first sense bacterial cells once they penetrate mucosal barriers and, following interaction with bacterial ligands, they produce large quantities of inflammatory mediators involved in the recruitment of neutrophils, as well as in T-cell activation and differentiation [38,39]. Inflammatory monocytes, involved in the clearance of ST258-KP infection in mice, [40,41] also may produce high amounts of inflammatory (TNFα, IL-1β) or anti-inflammatory cytokines [42,43]. …”

Section: Discussionmentioning

confidence: 99%

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

et al. 2017

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ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1β gene expression through p38MAPK- and NF-κB-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.

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“…Finally, several DTR based systems for the depletion of monocytes and macrophages (reviewed in (Lauvau et al, 2015)), have been generated that are driven by genes such as CCR2 and CX3CR1. These have helped segregate the independent functions of monocytes and cDCs.…”

Section: Mouse Models For Studying Dendritic Cellsmentioning

confidence: 99%

Functions of Murine Dendritic Cells

2016

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Dendritic cells (DCs) play critical roles in activating innate immune cells and initiating adaptive immune responses. The functions of DCs were originally obscured by their overlap with other mononuclear phagocytes, but new mouse models have allowed for the selective ablation of subsets of DCs and have helped to identify their non-redundant roles in the immune system. These tools have elucidated the functions of DCs in host defense against pathogens, autoimmunity, and cancer. This review will describe the mouse models generated to interrogate the role of DCs, and will discuss how their use has progressively clarified our understanding of the unique functions of DC subsets.

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Monocyte-mediated defense against bacteria, fungi, and parasites

Cited by 59 publications

References 154 publications

Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans

Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

Functions of Murine Dendritic Cells

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