Myeloid-related protein-8/14 facilitates bacterial growth during pneumococcal pneumonia

Achouiti, Ahmed; Vogl, Thomas; Endeman, Henrik; Mortensen, Brittany L.; Laterre, Pierre‐François; Wittebole, Xavier; Zoelen, Marieke A. D. van; Zhang, Yaofang; Hoogerwerf, Jacobien J.; Florquin, Sandrine; Schultz, Marcus J.; Grutters, Jan C.; Biesma, Douwe H.; Roth, Johannes; Skaar, Eric P.; Veer, Cornelis van ’t; Vos, Alex F. de; Poll, Tom van der

doi:10.1136/thoraxjnl-2014-205668

Cited by 36 publications

(40 citation statements)

References 39 publications

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“…Human pneumonia is associated with local and systemic MRP8/14 release [36,37], which correlates with findings in murine pneumonia caused by Klebsiella pneumoniae [20] or pneumococci [14,37]. In accordance, in the current model of S. aureus pneumonia, MRP8/14 levels in plasma and lungs were also increased.…”

Section: Discussionsupporting

confidence: 88%

“…The gradual increase of bronchoalveolar MRP8/14, which was at least 20 times higher than in Klebsiella pneumonia [20], might have been due to accumulation of released MRP8/14 after a massive early influx of activated neutrophils, which represent a major source of this protein [38,39]. We previously showed that MRP8 and the neutrophil marker Ly-6G have a similar expression in pneumococci infected lungs [37].…”

Section: Discussionmentioning

confidence: 99%

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Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

et al. 2015

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Staphylococcus aureus has evolved as an important cause of pneumonia in both hospital and community settings. Staphylococcal lung infection can lead to overwhelming pulmonary inflammation. During infection, neutrophils release complexes of myeloid-related protein (MRP)8 and MRP14 (MRP8/ 14). MRP8/14 has been shown to exert pro-inflammatory and chemotactic activity, and to assist in the killing of S. aureus. In the current study we sought to determine the role of MRP8/14 in the host response during S. aureus pneumonia.Pneumonia was induced in wildtype and MRP14-deficient mice (mice unable to form MRP8/14) by intranasal inoculation of 1×10 7 CFU of S. aureus USA300. Mice were sacrificed at 6, 24, 48 or 72 h after infection for analyses.S. aureus pneumonia was associated with a strong rise in MRP8/14 in bronchoalveolar lavage fluid and lung tissue. Surprisingly, MRP14 deficiency had a limited effect on bacterial clearance and was associated with increased cytokine levels in bronchoalveolar lavage fluid and aggravated lung histopathology. MRP14 deficiency in addition was associated with a diminished transmigration of neutrophils into bronchoalveolar lavage fluid at late time-points after infection together with reduced release of nucleosomes.MRP8/14 serves in an unexpected protective role for the lung in staphylococcal pneumonia. @ERSpublications MRP8/14 unexpectedly protects against excessive pulmonary inflammation in murine staphylococcal pneumonia http://ow.ly/IwYt6

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

et al. 2015

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“…49 Intriguingly, two different studies investigating the interactions between pneumococci and CP proposed conflicting roles for CP. 58, 59 In one study, increased pneumococcal survival and virulence was observed in CP-deficient mice compared to WT mice, suggesting a protective role for CP against pneumococci in mouse model of intranasal infection. 59 In another study using an identical mouse model of pneumococcal infection, the absence of CP in the knockout mouse caused defects in bacterial survival, disease dissemination, and virulence, prompting to speculate that CP facilitates pneumococcal infection.…”

Section: Host-imposed Zinc Limitation During Gas Infectionmentioning

confidence: 99%

“…59 In another study using an identical mouse model of pneumococcal infection, the absence of CP in the knockout mouse caused defects in bacterial survival, disease dissemination, and virulence, prompting to speculate that CP facilitates pneumococcal infection. 58 Additional studies are required to clarify the role of CP in host defense against pneumococcal invasion. Furthermore, investigations into the roles of pneumococcal zinc transporters in bacterial resistance against CP and in bacterial survival in wild type or CP-deficient mice will likely reveal the contribution of zinc chelation properties of CP to host defense against pneumococcal invasion.…”

Section: Host-imposed Zinc Limitation During Gas Infectionmentioning

confidence: 99%

Zinc’ing it out: zinc homeostasis mechanisms and their impact on the pathogenesis of human pathogen group A streptococcus

Makthal

Kumaraswami

2017

Metallomics

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Group A Streptococccus (GAS) is a major human pathogen that causes significant morbidity and mortality. Zinc is an essential trace element required for GAS growth, however, zinc can be toxic at excess concentration. The bacterial strategies to maintain zinc sufficiency without incurring zinc toxicity plays a crucial role in host-GAS interactions and has significant impact on GAS pathogenesis. Host deploys nutritional immune mechanisms to retard GAS growth by causing either zinc deprivation or zinc poisoning. However, GAS overcomes the zinc-dependent host defenses and survives in the hostile environment by employing complex adaptive strategies. In this review, we describe the different host immune strategies that employ either zinc limitation or zinc toxicity in different host environments to control GAS infection. We also discuss the molecular mechanisms and machineries used by GAS to evade host nutritional defenses and establish successful infection. Emerging evidence suggest that the metal transporters are major GAS virulence factors as they compete against host nutritional immune mechanisms to acquire or expel metals and promote bacterial survival in the host. Thus, identification of GAS molecules and elucidation of the mechanisms by which GAS combats host-mediated alterations in zinc availability may lead to novel interference strategies targeting GAS metal acquisition systems.

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“…Neutrophils provide host immunity to Streptococcus pneumonia via a number of pathways. However, a series of studies in patients with community-acquired pneumonia and mechanistic studies in a mouse model have revealed that one such pathway has been subverted by the bacteria to facilitate bacterial growth rather than clearance 12. In contrast to previous reports which outline a host protective role for the neutrophil-derived myeloid related protein (MRP) 8/14, Achouiti and colleagues determined that patients with community-acquired pneumonia (CAP) showed high levels of MRP 8/14 and that mice deficient in MRP14 exhibited reduced bacterial growth and improved survival—a prime example of how a bacterium can manipulate the immune system for its own benefit.…”

Section: Basic Sciencementioning

confidence: 99%

Year in review 2014: basic science and epidemiology

Lloyd

Cullinan

2015

Thorax

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Myeloid-related protein-8/14 facilitates bacterial growth during pneumococcal pneumonia

Cited by 36 publications

References 39 publications

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

Myeloid-related protein-14 deficiency promotes inflammation in staphylococcal pneumonia

Zinc’ing it out: zinc homeostasis mechanisms and their impact on the pathogenesis of human pathogen group A streptococcus

Year in review 2014: basic science and epidemiology

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