Viewing entries in
Host-Pathogen Interaction

Different Behavior and Response of Staphylococcus Epidermidis and Streptococcus Pneumoniaeto a Ventriculoperitoneal Shunt: An in vitro Study.

Pediatr Neurosurg. 2017;52(4):257-260. doi: 10.1159/000477817. Epub 2017 Jul 14.

Different Behavior and Response of Staphylococcus Epidermidis and Streptococcus Pneumoniaeto a Ventriculoperitoneal Shunt: An in vitro Study.

Heidari V1, Habibi ZHojjati Marvasti AEbrahim Soltani ZNaderian NTanzifi PNejat F.

Author information

Abstract

BACKGROUND:

Pneumococcal shunt infection is a rare event. There is no consensus on the therapeutic management of this kind of shunt infection according to literature reviews, and it seems to be different from infection with Staphylococcus epidermidis. We studied 2 shunted patients with pneumococcal meningitis, both of whom were treated with only antibiotics. The management of these cases seems to be different from that of shunt catheter infection due to these bacteria. We conducted a laboratory study to show the different behavior of pneumococcus compared to S. epidermidis regarding shunt catheter colonization.

MATERIALS AND METHODS:

S. epidermidis and Streptococcus pneumoniae bacteria isolated from the cerebrospinal fluid of meningitis patients were incubated in sterile media. Forty-five segments of shunt catheter from silicone material were placed in 45 separate media of S. epidermidis and pneumococcus. Then each catheter was washed and cultured in blood chocolate agar growth medium in separate petri dishes via the roll plate method. The dishes were extracted from the incubator and the colony count was calculated after 72 h.

RESULTS:

The colony count was obviously different between the 2 bacteria groups, with a higher count related to S. epidermidis dishes. The colony count of the pneumococcal petri dishes was 25-35,000 (mean 14,337) and for dishes with S. epidermidis it was 14,000-100,000 (mean 50,125) (p = 0.001).

CONCLUSION:

The adherence of pneumococcus to shunt catheters seems to be much less than that of S. epidermidis, which produced a very low colony count when incubated with the catheter in the medium culture. S. pneumoniae meningitis in shunted patients can be managed successfully with only antibiotics. This approach can prevent problems related to the several additional surgeries required for shunt removal, a new shunt insertion, and the management of high intracranial pressure.

© 2017 S. Karger AG, Basel.

KEYWORDS:

Colonization; Infection; Staphylococcus epidermidis; Streptococcus pneumoniae; Treatment; Ventriculoperitoneal shunt

PMID: 28704823 DOI: 10.1159/000477817

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro.

Front Cell Infect Microbiol. 2017 Jun 22;7:263. doi: 10.3389/fcimb.2017.00263. eCollection 2017.

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro.

Ngo Ndjom CG1, Kantor LV2, Jones HP1.

Author information

Abstract

Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28-50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH-pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock.

KEYWORDS:

Streptococcus pneumoniae; corticotropin releasing hormone; phenotype; sepsis virulence; serotypes

PMID: 28690980 PMCID: PMC5479890 DOI: 10.3389/fcimb.2017.00263

Mucin 1 protects against severe Streptococcus pneumoniae infection.

Virulence. 2017 Jun 12:0. doi: 10.1080/21505594.2017.1341021. [Epub ahead of print]

Mucin 1 protects against severe Streptococcus pneumoniae infection.

Dhar P1,2, Ng GZ1,2, Dunne EM1, Sutton P1,2,3.

Author information

Abstract

Streptococcus pneumoniae is a bacterial pathogen that commonly resides in the human nasopharynx, typically without causing any disease. However, in some cases these bacteria migrate from the nasopharynx to other sites of the body such as the lungs and bloodstream causing pneumonia and sepsis, respectively. This study used a mouse model of infection to investigate the potential role of Mucin 1 (MUC1), a cell membrane-associated glycoprotein known for playing a key barrier role at mucosal surfaces, in regulating this process. Wildtype (WT) and MUC1-deficient (Muc1-/-) mice were infected intranasally with an invasive strain of S. pneumoniae and bacterial loads in the nasopharynx, lungs, and blood were analyzed. Lungs were graded histologically for inflammation and cytokine profiles in the lungs analyzed by ELISA. While there was no difference in pneumococcal colonization of the nasopharynx between WT and Muc1-/- mice, infected Muc1-/- mice showed high pneumococcal loads in their lungs 16 hours post-infection, as well as bacteremia. In contrast, infected WT mice cleared the pneumococci from their lungs and remained asymptomatic. Infection in Muc1-/- mice was associated with an elevation in lung inflammation, with cellular recruitment especially of monocytes/macrophages. While MUC1-deficiency has been shown to increase phagocytosis of Pseudomonas aeruginosa, macrophages from Muc1-/- mice exhibited a reduced capacity to phagocytose S. pneumoniae indicating diverse and bacterial-specific effects. In conclusion, these findings indicate that MUC1 plays an important role in protection against severe pneumococcal disease, potentially mediated by facilitating macrophage phagocytosis.

KEYWORDS:

Muc1; Streptococcus pneumoniae; bacteremia; inflammation; macrophages; phagocytosis

PMID: 28605238 DOI: 10.1080/21505594.2017.1341021

T Cell-Mediated Humoral Immune Responses to Type 3 Capsular Polysaccharide of Streptococcus pneumoniae.

J Immunol. 2017 May 31. pii: 1700026. doi: 10.4049/jimmunol.1700026. [Epub ahead of print]

T Cell-Mediated Humoral Immune Responses to Type 3 Capsular Polysaccharide of Streptococcus pneumoniae.

Middleton DR1, Sun L1, Paschall AV1, Avci FY2.

Author information

Abstract

Most pathogenic bacteria express surface carbohydrates called capsular polysaccharides (CPSs). CPSs are important vaccine targets because they are easily accessible and recognizable by the immune system. However, CPS-specific adaptive humoral immune responses can only be achieved by the covalent conjugation of CPSs with carrier proteins to produce glycoconjugate vaccines. We previously described a mechanism by which a model glycoconjugate vaccine can activate the adaptive immune system and demonstrated that the mammalian CD4+ T cell repertoire contains a population of carbohydrate-specific T cells. In this study, we use glycoconjugates of type 3 Streptococcus pneumoniae CPS (Pn3P) to assess whether the carbohydrate-specific adaptive immune response exemplified in our previous study can be applied to the conjugates of this lethal pathogen. In this article, we provide evidence for the functional roles of Pn3P-specific CD4+ T cells utilizing mouse immunization schemes that induce Pn3P-specific IgG responses in a carbohydrate-specific T cell-dependent manner.

Copyright © 2017 by The American Association of Immunologists, Inc.

PMID: 28566369 DOI: 10.4049/jimmunol.1700026

Proteomic variation and diversity in clinical Streptococcus pneumoniaeisolates from invasive and non-invasive sites.

PLoS One. 2017 Jun 2;12(6):e0179075. doi: 10.1371/journal.pone.0179075. eCollection 2017.

Proteomic variation and diversity in clinical Streptococcus pneumoniaeisolates from invasive and non-invasive sites.

Bittaye M1, Cash P1, Forbes K1.

Author information

Abstract

Streptococcus pneumoniae is responsible for a variety of invasive and non-invasive human infections. There are over 90 serotypes of S. pneumoniae differing in their ability to adapt to the different niches within the host. Two-dimensional gel electrophoresis was used to discriminate clinical S. pneumoniae isolates recovered from either blood cultures (invasive site isolates) or other sites, including sputum, tracheal aspirate, ear, eye and skin swabs (non-invasive site isolates). Global protein expression profiles for five invasive site and six non-invasive site isolates representing five different serotypes (serotypes 4, 6, 9, 14 and 23) were obtained for each isolate and combined into a single data set using Progenesis SameSpots™ software. One-hundred and eighty six protein spots (39% of the protein spots in the dataset) differed significantly (ANOVA, p<0.05) in abundance between the invasive site (101 upregulated protein spots) and non-invasive site (85 upregulated protein spots) isolates. Correlations between the bacterial proteomes and their sites of isolation were determined by Principal Component Analysis (PCA) using the significantly different protein spots. Out of the 186 variable protein spots, 105 exhibited a serotype-associated pattern of variability. The expression of the remaining 81 protein spots was concluded to be uniquely linked to the site of bacterial isolation. Mass spectrometry was used to identify selected protein spots that showed either constant or differential abundance levels. The identified proteins had a diverse range of functions including, capsule biogenesis, DNA repair, protein deglycation, translation, stress response and virulence as well as amino acid, carbohydrate, lipid and nucleotide metabolism. These findings provide insight on the proteins that contribute towards the adaptation of the bacteria to different sites within the host.

PMID: 28575057 PMCID: PMC5456405 DOI: 10.1371/journal.pone.0179075

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

Clin Infect Dis. 2017 Jun 15;64(suppl_3):S317-S327. doi: 10.1093/cid/cix100.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

Baggett HC1,2, Watson NL3, Deloria Knoll M4, Brooks WA5,6, Feikin DR4,7, Hammitt LL4,8, Howie SRC9,10,11, Kotloff KL12, Levine OS4,13, Madhi SA14,15, Murdoch DR16,17, Scott JAG8,18, Thea DM19, Antonio M9,20,21, Awori JO8, Baillie VL14,15, DeLuca AN4,22, Driscoll AJ4, Duncan J23, Ebruke BE9, Goswami D6, Higdon MM4, Karron RA24, Moore DP14,15,25, Morpeth SC8,18,26, Mulindwa JM23, Park DE4,27, Paveenkittiporn W28, Piralam B29, Prosperi C4, Sow SO30, Tapia MD12, Zaman K6, Zeger SL31, O'Brien KL4; PERCH Study Group.

Collaborators (73)

 

 

Author information

Abstract

BACKGROUND.:

Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association.

METHODS.:

PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens.

RESULTS.:

Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001).

CONCLUSIONS.:

Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

KEYWORDS:

children; colonization; etiology; pneumococcus; pneumonia

PMID: 28575365 DOI: 10.1093/cid/cix100

Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.

mSphere. 2017 Jun 7;2(3). pii: e00201-17. doi: 10.1128/mSphere.00201-17. eCollection 2017 May-Jun.

Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.

Rieger M1, Mauch H2, Hakenbeck R1.

Author information

Abstract

Streptococcus pneumoniae isolates of serotype 23F with intermediate penicillin resistance were recovered on seven occasions over a period of 37 months from a cystic fibrosis patient in Berlin. All isolates expressed the same multilocus sequence type (ST), ST10523. The genome sequences of the first and last isolates, D122 and D141, revealed the absence of two phage-related gene clusters compared to the genome of another ST10523 strain, D219, isolated earlier at a different place in Germany. Genomes of all three strains carried the same novel mosaic penicillin-binding protein (PBP) genes, pbp2xpbp2b, and pbp1a; these genes were distinct from those of other penicillin-resistant S. pneumoniae strains except for pbp1a of a Romanian S. pneumoniae isolate. All PBPs contained mutations that have been associated with the penicillin resistance phenotype. Most interestingly, a mosaic block identical to an internal pbp2xsequence of ST10523 was present in pbp2x of Streptococcus mitis strain B93-4, which was isolated from the same patient. This suggests interspecies gene transfer from S. pneumoniae to S. mitis within the host. Nearly all genes expressing surface proteins, which represent major virulence factors of S. pneumoniaeand are typical for this species, were present in the genome of ST10523. One exception was the hyaluronidase gene hlyA, which contained a 12-nucleotide deletion within the promoter region and an internal stop codon. The lack of a functional hyaluronidase might contribute to the ability to persist in the host for an unusually long period of time. IMPORTANCEStreptococcus pneumoniae is a common resident in the human nasopharynx. However, carriage can result in severe diseases due to a unique repertoire of pathogenicity factors that are rare in closely related commensal streptococci. We investigated a penicillin-resistant S. pneumoniae clone of serotype 23F isolated from a cystic fibrosis patient on multiple occasions over an unusually long period of over 3 years that was present without causing disease. Genome comparisons revealed an apparent nonfunctional pneumococcus-specific gene encoding a hyaluronidase, supporting the view that this enzyme adds to the virulence potential of the bacterium. The 23F clone harbored unique mosaic genes encoding penicillin resistance determinants, the product of horizontal gene transfer involving the commensal S. mitis as donor species. Sequences identical to one such mosaic gene were identified in an S. mitis strain from the same patient, suggesting that in this case S. pneumoniaeplayed the role of donor.

KEYWORDS:

23F clone; Streptococcus pneumoniae; cystic fibrosis; hyaluronidase; penicillin-binding proteins; persistence

PMID: 28596991 PMCID: PMC5463027 DOI: 10.1128/mSphere.00201-17

The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.

Front Cell Infect Microbiol. 2017 May 3;7:161. doi: 10.3389/fcimb.2017.00161. eCollection 2017.

The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.

Bou Ghanem EN1, Lee JN1, Joma BH2, Meydani SN3, Leong JM1, Panda A3.

Author information

Abstract

Despite the availability of vaccines, Streptococcus pneumoniae remains a leading cause of life-threatening infections, such as pneumonia, bacteremia and meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease course, because optimal host defense requires an initial robust pulmonary PMN response to control bacterial numbers followed by modulation of this response later in infection. The elderly, who manifest a general decline in immune function and higher basal levels of inflammation, are at increased risk of developing pneumococcal pneumonia. Using an aged mouse infection model, we previously showed that oral supplementation with the alpha-tocopherol form of vitamin E (α-Toc) decreases pulmonary inflammation, in part by modulating neutrophil migration across lung epithelium into alveolar spaces, and reverses the age-associated decline in resistance to pneumococcal pneumonia. The objective of this study was to test the effect of α-Toc on the ability of neutrophils isolated from young (22-35 years) or elderly (65-69 years) individuals to migrate across epithelial cell monolayers in response to S. pneumoniae and to kill complement-opsonized pneumococci. We found that basal levels of pneumococcal-induced transepithelial migration by PMNs from young or elderly donors were indistinguishable, suggesting that the age-associated exacerbation of pulmonary inflammation is not due to intrinsic properties of PMNs of elderly individuals but rather may reflect the inflammatory milieu of the aged lung. Consistent with its anti-inflammatory activity, α-Toc treatment diminished PMN migration regardless of donor age. Unexpectedly, unlike previous studies showing poor killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were more efficient at killing complement-opsonized bacteria ex vivo than their younger counterparts. We also found that the heightened antimicrobial activity in PMNs from older donors correlated with increased activity of neutrophil elastase, a serine protease that is required to kill pneumococci. Notably, incubation with α-Toc increased PMN elastase activity from young donors and boosted their ability to kill complement-opsonized pneumococci. These findings demonstrate that α-Toc is a potent modulator of PMN responses and is a potential nutritional intervention to combat pneumococcal infection.

KEYWORDS:

S. pneumoniae; aging; infection; inflammation; neutrophils; serine proteases; vitamin E

PMID: 28516066 PMCID: PMC5413490 DOI: 10.3389/fcimb.2017.00161

Role of neural barriers in the pathogenesis and outcome of Streptococcus pneumoniae meningitis.

Exp Ther Med. 2017 Mar;13(3):799-809. doi: 10.3892/etm.2017.4082. Epub 2017 Jan 24.

Role of neural barriers in the pathogenesis and outcome of Streptococcus pneumoniae meningitis.

Prager O1,2, Friedman A1,2,3, Nebenzahl YM4.

Author information

Abstract

Bacterial meningitis is an inflammatory disease of the meninges of the central nervous system (CNS). Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis, and Haemophilus influenzae are the major bacterial pathogens causing meningitis with S. pneumoniae being responsible for two thirds of meningitis cases in the developed world. To reach the CNS following nasopharyngeal colonization and bacteraemia, the bacteria traverse from the circulation across the blood brain barrier (BBB) and choroid plexus. While the BBB has a protective role in healthy individuals by shielding the CNS from neurotoxic substances circulating in the blood and maintaining the homeostasis within the brain environment, dysfunction of the BBB is associated with the pathophysiology of numerous neurologic disorders, including bacterial meningitis. Inflammatory processes, including release of a broad range of cytokines and free radicals, further increase vascular permeability and contribute to the excessive neural damage observed. Injury to the cerebral microvasculature and loss of blood flow auto-regulation promote increased intracranial pressure and may lead to vascular occlusion. Other common complications commonly associated with meningitis include abnormal neuronal hyper-excitability (e.g., seizures) and loss of hearing. Despite the existence of antibiotic treatment and adjuvant therapy, the relatively high mortality rate and the severe outcomes among survivors of pneumococcal meningitis in developing and developed countries increase the urgency in the requirement of discovering novel biomarkers for the early diagnosis as well as novel treatment approaches. The present review aimed to explore the changes in the brain vascular barriers, which allow S. pneumoniae to invade the CNS, and describe the resultant brain injuries following bacterial meningitis.

KEYWORDS:

S. pneumoniae; blood brain barrier; central nervous system; inflammation; innate immunity; meningitis; pathogenesis; virulence factors

PMID: 28450902 PMCID: PMC5403536 DOI: 10.3892/etm.2017.4082

Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.

Microbiol Immunol. 2017 May 2. doi: 10.1111/1348-0421.12487. [Epub ahead of print]

Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.

Kataoka K1, Fukuyama Y2, Briles DE2, Miyake T1, Fujihashi K2.

Author information

Abstract

In order to develop safe vaccines for effective mucosal immunity to major pulmonary bacterial infections, one must consider appropriate vaccine antigens (Ags), delivery systems and nontoxic molecular adjuvants. Such vaccine constructs can induce Ag-specific immune responses which provide effective protection from mucosal infections. In particular, it has been shown that adjuvant-based mucosal vaccine preparations are relatively easy to construct by simply mixing the adjuvant with the bacterial Ag, and the resulting vaccine can elicit protective immunity. We have studied DNA-based nasal adjuvants targeting mucosal dendritic cells (DCs) in order to induce Ag-specific mucosal and systemic immune responses that provide essential protection against microbial pathogens which invade our mucosal surfaces. In this review, we initially introduce a plasmid encoding the cDNA of Flt3 ligand (pFL), a molecule which is a growth factor for DCs as an effective adjuvant for mucosal immunity to pneumococcal infections. Next, we discuss the potential of adding unmethylated CpG oligodeoxynucleotide together with pFL together with a pneumococcal Ag for protection from pneumococcal infections. To do this, we have used pneumococcal surface protein A as vaccine for the restoration of mucosal immunity in aging. Further, we have also used our nasal pFL adjuvant system with phosphorylcholine-keyhole limpet hemocyanin (PC-KLH) in pneumococcal vaccine development, to successfully induce complete protection from nasal carriage by Streptococcus pneumoniae. Finally, we discuss the possibility that anti-PC antibodies induced by nasal delivery of pFL plus PC-KLH may play a protective role for prevention of atherogenesis and thus block the subsequent development of cardiovascular disease.

© 2017 The Societies and Wiley Publishing Asia Pty Ltd.

KEYWORDS:

DNA-based adjuvants; Dendritic cells; Nasal vaccination; Streptococcus pneumoniae

PMID: 28463465 DOI: 10.1111/1348-0421.12487

Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.

Innate Immun. 2017 Apr;23(3):219-227. doi: 10.1177/1753425916684934. Epub 2016 Dec 20.

Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.

Salina AC1, Souza TP1, Serezani CH2, Medeiros AI1.

Author information

Abstract

Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE2) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.

KEYWORDS:

Efferocytosis; Streptococcus pneumoniae; alveolar macrophages; apoptotic cells; prostaglandin E2

PMID: 28359217 DOI: 10.1177/1753425916684934

The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae.

Innate Immun. 2017 Jan 1:1753425917704299. doi: 10.1177/1753425917704299. [Epub ahead of print]

The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae.

Ullah I1, Ritchie ND1, Evans TJ1.

Author information

Abstract

Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.

KEYWORDS:

Autophagy; Streptococcus pneumoniae; bacterial killing; neutrophil extracellular trap; pneumolysin

PMID: 28399692 DOI: 10.1177/1753425917704299