#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Innate Killing of by Macrophages of the Splenic Marginal Zone Requires IRF-7


Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.


Vyšlo v časopise: Innate Killing of by Macrophages of the Splenic Marginal Zone Requires IRF-7. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000813
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000813

Souhrn

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.


Zdroje

1. HumeDA

RossIL

HimesSR

SasmonoRT

WellsCA

2002 The mononuclear phagocyte system revisited. J Leukoc Biol 72 621 627

2. RavasiT

WellsCA

HumeDA

2007 Systems biology of transcription control in macrophages. Bioessays 29 1215 1226

3. WellsCA

RavasiT

FaulknerGJ

CarninciP

OkazakiY

2003 Genetic control of the innate immune response. BMC Immunol 4 5

4. GordonS

TaylorPR

2005 Monocyte and macrophage heterogeneity. Nat Rev Immunol 5 953 964

5. MebiusRE

KraalG

2005 Structure and function of the spleen. Nat Rev Immunol 5 606 616

6. AtoM

NakanoH

KakiuchiT

KayePM

2004 Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19. J Immunol 173 4815 4820

7. GeijtenbeekTB

GrootPC

NolteMA

van VlietSJ

Gangaram-PandayST

2002 Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. Blood 100 2908 2916

8. KraalG

JanseM

1986 Marginal metallophilic cells of the mouse spleen identified by a monoclonal antibody. Immunology 58 665 669

9. KraalG

MebiusR

2006 New insights into the cell biology of the marginal zone of the spleen. Int Rev Cytol 250 175 215

10. SeilerP

AicheleP

OdermattB

HengartnerH

ZinkernagelRM

1997 Crucial role of marginal zone macrophages and marginal zone metallophils in the clearance of lymphocytic choriomeningitis virus infection. Eur J Immunol 27 2626 2633

11. FranzosoG

CarlsonL

PoljakL

ShoresEW

EpsteinS

1998 Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture. J Exp Med 187 147 159

12. WeihDS

YilmazZB

WeihF

2001 Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol 167 1909 1919

13. KoppelEA

WielandCW

van den BergVC

LitjensM

FlorquinS

2005 Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcus pneumoniae infection. Eur J Immunol 35 2962 2969

14. LanoueA

ClatworthyMR

SmithP

GreenS

TownsendMJ

2004 SIGN-R1 contributes to protection against lethal pneumococcal infection in mice. J Exp Med 200 1383 1393

15. AicheleP

ZinkeJ

GrodeL

SchwendenerRA

KaufmannSH

2003 Macrophages of the splenic marginal zone are essential for trapping of blood-borne particulate antigen but dispensable for induction of specific T cell responses. J Immunol 171 1148 1155

16. KoppelEA

LitjensM

van den BergVC

van KooykY

GeijtenbeekTB

2008 Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B cells is essential to early IgM responses against Streptococcus pneumoniae. Mol Immunol 45 2881 2887

17. GorakPM

EngwerdaCR

KayePM

1998 Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection. Eur J Immunol 28 687 695

18. ElorantaML

AlmGV

1999 Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus. Scand J Immunol 49 391 394

19. CrockerPR

GordonS

1985 Isolation and characterization of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow. J Exp Med 162 993 1014

20. CarrascoYR

BatistaFD

2007 B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27 160 171

21. JuntT

MosemanEA

IannaconeM

MassbergS

LangPA

2007 Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450 110 114

22. PhanTG

GrigorovaI

OkadaT

CysterJG

2007 Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat Immunol 8 992 1000

23. ZiporiD

FriedmanA

TamirM

SilverbergD

MalikZ

1984 Cultured mouse marrow cell lines: interactions between fibroblastoid cells and monocytes. J Cell Physiol 118 143 152

24. EngwerdaCR

SmeltSC

KayePM

1996 An in vivo analysis of cytokine production during Leishmania donovani infection in scid mice. Exp Parasitol 84 195 202

25. Alter-KoltunoffM

GorenS

NousbeckJ

FengCG

SherA

2008 Innate immunity to intraphagosomal pathogens is mediated by interferon regulatory factor 8 (IRF-8) that stimulates the expression of macrophage-specific Nramp1 through antagonizing repression by c-Myc. J Biol Chem 283 2724 2733

26. IshidaY

HayashiT

GotoT

KimuraA

AkimotoS

2008 Essential involvement of CX3CR1-mediated signals in the bactericidal host defense during septic peritonitis. J Immunol 181 4208 4218

27. WillmentJA

BrownGD

2008 C-type lectin receptors in antifungal immunity. Trends Microbiol 16 27 32

28. WellsCA

Salvage-JonesJA

LiX

HitchensK

ButcherS

2008 The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180 7404 7413

29. PluddemannA

HoeJC

MakepeaceK

MoxonER

GordonS

2009 The macrophage scavenger receptor a is host-protective in experimental meningococcal septicaemia. PLoS Pathog 5 e1000297 doi:10.1371/journal.ppat.1000297

30. SanoH

IshinoM

KramerH

ShimizuT

MitsuzawaH

2007 The microtubule-binding protein Hook3 interacts with a cytoplasmic domain of scavenger receptor A. J Biol Chem 282 7973 7981

31. KrakowiakPA

WassifCA

KratzL

CozmaD

KovarovaM

2003 Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet 12 1631 1641

32. ChakrabortyD

BanerjeeS

SenA

BanerjeeKK

DasP

2005 Leishmania donovani affects antigen presentation of macrophage by disrupting lipid rafts. J Immunol 175 3214 3224

33. RubA

DeyR

JadhavM

KamatR

ChakkaramakkilS

2009 Cholesterol depletion associated with Leishmania major infection alters macrophage CD40 signalosome composition and effector function. Nat Immunol 10 273 280

34. McKnightAJ

GordonS

1998 The EGF-TM7 family: unusual structures at the leukocyte surface. J Leukoc Biol 63 271 280

35. ShamirR

Maron-KatzA

TanayA

LinhartC

SteinfeldI

2005 EXPANDER–an integrative program suite for microarray data analysis. BMC Bioinformatics 6 232

36. ElkonR

LinhartC

SharanR

ShamirR

ShilohY

2003 Genome-wide in silico identification of transcriptional regulators controlling the cell cycle in human cells. Genome Res 13 773 780

37. HondaK

YanaiH

NegishiH

AsagiriM

SatoM

2005 IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434 772 777

38. ColinaR

Costa-MattioliM

DowlingRJ

JaramilloM

TaiLH

2008 Translational control of the innate immune response through IRF-7. Nature 452 323 328

39. HondaK

OhbaY

YanaiH

NegishiH

MizutaniT

2005 Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434 1035 1040

40. DiefenbachA

SchindlerH

DonhauserN

LorenzE

LaskayT

1998 Type 1 interferon (IFNalpha/beta) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity 8 77 87

41. BogdanC

RollinghoffM

DiefenbachA

2000 The role of nitric oxide in innate immunity. Immunol Rev 173 17 26

42. HataN

SatoM

TakaokaA

AsagiriM

TanakaN

2001 Constitutive IFN-alpha/beta signal for efficient IFN-alpha/beta gene induction by virus. Biochem Biophys Res Commun 285 518 525

43. LefkirY

MalbouyresM

GotthardtD

OzinskyA

CornillonS

2004 Involvement of the AP-1 adaptor complex in early steps of phagocytosis and macropinocytosis. Mol Biol Cell 15 861 869

44. De Souza LeaoS

LangT

PrinaE

HellioR

AntoineJC

1995 Intracellular Leishmania amazonensis amastigotes internalize and degrade MHC class II molecules of their host cells. J Cell Sci 108 ( Pt 10) 3219 3231

45. LangT

HellioR

KayePM

AntoineJC

1994 Leishmania donovani-infected macrophages: characterization of the parasitophorous vacuole and potential role of this organelle in antigen presentation. J Cell Sci 107 ( Pt 8) 2137 2150

46. BlackwellJM

GoswamiT

EvansCA

SibthorpeD

PapoN

2001 SLC11A1 (formerly NRAMP1) and disease resistance. Cell Microbiol 3 773 784

47. SchleicherU

LieseJ

KnippertzI

KurzmannC

HesseA

2007 NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs. J Exp Med 204 893 906

48. LieseJ

SchleicherU

BogdanC

2007 TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis. Eur J Immunol 37 3424 3434

49. StagerS

AlexanderJ

KirbyAC

BottoM

RooijenNV

2003 Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses. Nat Med 9 1287 1292

50. TsagozisP

KaragouniE

DotsikaE

2005 Function of CD8+ T lymphocytes in a self-curing mouse model of visceral leishmaniasis. Parasitol Int 54 139 146

51. StagerS

KayePM

2004 CD8+ T-cell priming regulated by cytokines of the innate immune system. Trends Mol Med 10 366 371

52. Le BonA

ToughDF

2008 Type I interferon as a stimulus for cross-priming. Cytokine Growth Factor Rev 19 33 40

53. QuerecTD

AkondyRS

LeeEK

CaoW

NakayaHI

2009 Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10 116 125

54. ReinerNE

NgW

McMasterWR

1987 Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J Immunol 138 1926 1932

55. GoubauD

Romieu-MourezR

SolisM

HernandezE

MespledeT

2009 Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7. Eur J Immunol 39 527 540

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 3
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#