#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Neutrophil-Derived CCL3 Is Essential for the Rapid Recruitment of Dendritic Cells to the Site of Inoculation in Resistant Mice


Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs) in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3−/− mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.


Vyšlo v časopise: Neutrophil-Derived CCL3 Is Essential for the Rapid Recruitment of Dendritic Cells to the Site of Inoculation in Resistant Mice. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000755
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000755

Souhrn

Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs) in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3−/− mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.


Zdroje

1. NathanC

2006 Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6 173 182

2. AppelbergR

2007 Neutrophils and intracellular pathogens: beyond phagocytosis and killing. Trends Microbiol 15 87 92

3. SacksD

Noben-TrauthN

2002 The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2 845 858

4. BeilWJ

Meinardus-HagerG

NeugebauerDC

SorgC

1992 Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J Leukoc Biol 52 135 142

5. Tacchini-CottierF

ZweifelC

BelkaidY

MukankundiyeC

VaseiM

2000 An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major. J Immunol 165 2628 2636

6. PetersNC

EgenJG

SecundinoN

DebrabantA

KimblinN

2008 In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321 970 974

7. Ribeiro-GomesFL

OteroAC

GomesNA

Moniz-De-SouzaMC

Cysne-FinkelsteinL

2004 Macrophage interactions with neutrophils regulate Leishmania major infection. J Immunol 172 4454 4462

8. McFarlaneE

PerezC

CharmoyM

AllenbachC

CarterKC

2008 Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani. Infect Immun 76 532 541

9. CharmoyM

MegnekouR

AllenbachC

ZweifelC

PerezC

2007 Leishmania major induces distinct neutrophil phenotypes in mice that are resistant or susceptible to infection. J Leukoc Biol 82 288 299

10. BaldwinT

HenriS

CurtisJ

O'KeeffeM

VremecD

2004 Dendritic cell populations in Leishmania major-infected skin and draining lymph nodes. Infect Immun 72 1991 2001

11. BrewigN

KissenpfennigA

MalissenB

VeitA

BickertT

2009 Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. J Immunol 182 774 783

12. SoongL

2008 Modulation of dendritic cell function by Leishmania parasites. J Immunol 180 4355 4360

13. StoitznerP

PfallerK

StosselH

RomaniN

2002 A close-up view of migrating Langerhans cells in the skin. J Invest Dermatol 118 117 125

14. ShklovskayaE

RoedigerB

Fazekas de St GrothB

2008 Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo. J Immunol 181 418 430

15. RandolphGJ

OchandoJ

Partida-SanchezS

2008 Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 26 293 316

16. LeonB

Lopez-BravoM

ArdavinC

2005 Monocyte-derived dendritic cells. Semin Immunol 17 313 318

17. DieuMC

VanbervlietB

VicariA

BridonJM

OldhamE

1998 Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 188 373 386

18. PowerCA

ChurchDJ

MeyerA

AlouaniS

ProudfootAE

1997 Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells. J Exp Med 186 825 835

19. SozzaniS

SallustoF

LuiniW

ZhouD

PiemontiL

1995 Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J Immunol 155 3292 3295

20. CassatellaMA

1999 Neutrophil-derived proteins: selling cytokines by the pound. Adv Immunol 73 369 509

21. LarsenCP

SteinmanRM

Witmer-PackM

HankinsDF

MorrisPJ

1990 Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med 172 1483 1493

22. BelkaidY

JouinH

MilonG

1996 A method to recover, enumerate and identify lymphomyeloid cells present in an inflammatory dermal site: a study in laboratory mice. J Immunol Methods 199 5 25

23. LeonB

Lopez-BravoM

ArdavinC

2007 Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26 519 531

24. FrauenschuhA

PowerCA

DeruazM

FerreiraBR

SilvaJS

2007 Molecular cloning and characterization of a highly selective chemokine-binding protein from the tick Rhipicephalus sanguineus. J Biol Chem 282 27250 27258

25. DeruazM

FrauenschuhA

AlessandriAL

DiasJM

CoelhoFM

2008 Ticks produce highly selective chemokine binding proteins with antiinflammatory activity. J Exp Med

26. SatoN

AhujaSK

QuinonesM

KosteckiV

ReddickRL

2000 CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med 192 205 218

27. YangD

ChenQ

ChertovO

OppenheimJJ

2000 Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol 68 9 14

28. KasamaT

StrieterRM

StandifordTJ

BurdickMD

KunkelSL

1993 Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1 alpha. J Exp Med 178 63 72

29. BennounaS

BlissSK

CurielTJ

DenkersEY

2003 Cross-talk in the innate immune system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection. J Immunol 171 6052 6058

30. AntoniaziS

PriceHP

KropfP

FreudenbergMA

GalanosC

2004 Chemokine gene expression in toll-like receptor-competent and -deficient mice infected with Leishmania major. Infect Immun 72 5168 5174

31. QuinonesMP

EstradaCA

JimenezF

MartinezH

WillmonO

2007 CCL2-independent role of CCR2 in immune responses against Leishmania major. Parasite Immunol 29 211 217

32. SantiagoHC

OliveiraCF

SantiagoL

FerrazFO

de SouzaDG

2004 Involvement of the chemokine RANTES (CCL5) in resistance to experimental infection with Leishmania major. Infect Immun 72 4918 4923

33. MorelC

BadellE

AbadieV

RobledoM

SetterbladN

2008 Mycobacterium bovis BCG-infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice. Eur J Immunol 38 437 447

34. van GisbergenKP

Sanchez-HernandezM

GeijtenbeekTB

van KooykY

2005 Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN. J Exp Med 201 1281 1292

35. EkenC

GasserO

ZenhaeusernG

OehriI

HessC

2008 Polymorphonuclear neutrophil-derived ectosomes interfere with the maturation of monocyte-derived dendritic cells. J Immunol 180 817 824

36. NgLG

HsuA

MandellMA

RoedigerB

HoellerC

2008 Migratory dermal dendritic cells act as rapid sensors of protozoan parasites. PLoS Pathog 4 e1000222 doi:10.1371/journal.ppat.1000222

37. RitterU

MeissnerA

ScheidigC

KornerH

2004 CD8 alpha- and Langerin-negative dendritic cells, but not Langerhans cells, act as principal antigen-presenting cells in leishmaniasis. Eur J Immunol 34 1542 1550

38. IezziG

FrohlichA

ErnstB

AmpenbergerF

SaelandS

2006 Lymph node resident rather than skin-derived dendritic cells initiate specific T cell responses after Leishmania major infection. J Immunol 177 1250 1256

39. ZhangN

SchroppelB

ChenD

FuS

HudkinsKL

2003 Adenovirus transduction induces expression of multiple chemokines and chemokine receptors in murine beta cells and pancreatic islets. Am J Transplant 3 1230 1241

40. InabaK

SteinmanRM

PackMW

AyaH

InabaM

1992 Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med 175 1157 1167

41. LopezAF

StrathM

SandersonCJ

1984 Differentiation antigens on mouse eosinophils and neutrophils identified by monoclonal antibodies. Br J Haematol 57 489 494

42. Tacchini-CottierF

AllenbachC

OttenLA

RadtkeF

2004 Notch1 expression on T cells is not required for CD4+ T helper differentiation. Eur J Immunol 34 1588 1596

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#