S. GORDON                                            FHS IMMUNOLOGY                                                            2003                                                                    

 

MACROPHAGES: Role in Innate & Acquired Immunity

 

Also see haematopoiesis, dendritic cells and cell-mediated immunity on other reading lists.

 

General    Life history, tissue distribution, cellular properties.

1.   Gordon 1998.  Macrophages and the immune response.  Fundamental

      Immunology.  4^th ed. W.  Paul, Chapter 15: 533-545.  5^th ed. In Press.

2.   S. Gordon 2001.  Immunology, Chapter 9, 6th ed. Roitt, Brostoff & Male.

3.   Gordon et al 1992. In: Macrophage biology and activation. Eds. Russell and Gordon. Springer Verlag. p1. Differentiation antigen markers and heterogeneity.

 

Growth and differentiation

Pu-1            Anderson et al, 1998.  Blood.  91: 3702-10.  Myeloid development disrupted in ko.

CSF-1         Wiktor Jedrzejczak & Gordon 1996. Physiol. Reviews 76: 927-47. CSF-1 and op/op mice. (also GM-CSF, IL-3).

GM-CSF      Inaba et al, 1992. J. Exp. Med. 175: 1157. MØ and DC differentiation in vitro.

                     Randolph et al.  1999. Immunity 11: 753-761.  Monocytic differentiation into DC in vivo by phagocytosis. 

 

Cell Recruitment - Chemokines and Receptors

Baggiolini 2001 Review J. Intern. Med. 250: 91-104.

 

Adhesion molecules, including CR3.

1.               Springer 1990 Nature 356: 425-434.

2.               Rosen and Gordon, 1987. J. Exp. Med. 166: 1685. Anti CR3 mAb blocks cell

                  recruitment in vivo.

3.                              Rosen et al, 1989, J. Exp. Med. 170: 27. CR3 in Listeria.

4.                              Fraser, Hughes & Gordon 1993. Nature 364: 343. Scavenger receptor (SR-A) and MØ adhesion.

 

Innate Immunity: 

1.               Janeway. Cold Spring Harbor Symp. Quant. Biol. LIV, 1989, p97.

2.               Fearon and Locksley 1996.  Science 272: 50-53.  Link adaptive immunity.

3.                Innate recognition systems (Forum in Immunology).  Microbes and infection.  2000 Vol 2  No.  3 (March) 239-336.                                                                              

                  (Covers pattern recognition receptors, Toll, CR3, lectins, CD14, scavenger receptor, inhibitory receptors, N-ramp and chemokines.)

4.               Barclay et al, 2002. Trends in Immunol. 213: 285-290.  (CD47, SIRP, CD200/R).

5.                              Colonna M. 2003. TREMs in the immune system and beyond. Nat Rev Immunol. 3:445-53.. 

 

Phagocytosis  

1.               Aderem & Underhill 1999. Ann. Rev. Imm. 17: 593-623.

2.              Caron & Hall 1998. Science 282: 1717-1721.  Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.

 

Phagocytosis of Apoptotic cells 

Platt et al 1996. SR-A apoptosis thymocytes PNAS 93: 12456-60.  Also - Platt & Gordon 2001. J. Clin. Invest.   108: 649-654. (Review).

Fadok et al, 2001. J. Clin. Invest. 108: 957-962. (PS receptor and responses).

Freire-de-Lima et al 2000.  Nature 403: 199.  Apoptotic cell uptake enhances intracellular pathogen. 

Albert et al 1998.  Nature 392: 86-.  Uptake of apoptotic cells by DC presents antigen to CTL;

Inaba K et al 1998 J Exp Med 188:2163-73. Efficient presentation of phagocytosed cellular fragments on the MHC II products of dendritic cells.

Larsson et al, 2001. Trends in Immunol. 22: 141.  (Review - cross presentation).

Gallucci, Lolkema & Matzinger 1999.  Nat Med 5: 1249-1255.  Natural adjuvants: endogenous activators of dendritic cells.  

Botto M et al 1998. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet. 19:56-9.

Bickerstaff MC et al 1999. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med 5:694-7. 

Taylor PR et al 2000. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med. 192:359-66. 

Scott RS et al 2001. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207-11. 

 

Toll-like receptors  

Imber and Hoffmann 2001.  Trends in Cell Biol. 11: 304-311.  (Drosophila, signals).    

Akira et al, 2001.  Nature Immunology 2: 675-676. (Mammalian)

Ozinsky 2000 PNAS 97: 13766-13771 (Co-operation between TLR)

Underhill et al 2000. Nature 401: 811-815. TLR2 recruited to phagosomes.

Medzhitov 2001. Nat. Immunol. 2: 828-835. TIRAP. 

Brown GD et al 2003. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 197:1119-24.

Gantner BN et al 2003. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 197:1107-17. 

 

Mannose receptors  

 

The MØ Mannose Receptor

Stahl PD & Ezekowitz RA 1998. The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol. 10:50-5. Review.

Linehan et al. 1999. J.Exp. Med. 189: 1961-1972; Linehan et al . Eur. J. Imm 31: 1857-1866.

Lee SJ et al 2002. Mannose receptor-mediated regulation of serum glycoprotein homeostasis.

Science. 295:1898-901.

 

DC-SIGN:

Geijtenbeek et al 2002. J. Leuk. Biol. 71: 921.

 

b-Glucan receptor. 

Brown & Gordon 2001. Immune recognition. A new receptor for beta-glucans. Nature 413: 36-37.

Brown & Gordon 2003. Fungal beta-glucans and mammalian immunity. Immunity 19:311-5.

 

CD1 family  

Porcelli et al.  1998.  Lipid Ag.  Immunol.  Today 19: 362-368.

 

Fc Receptors

Hogarth 2002. Curr. Opin. Immunol. 14: 798.

 

MØ activation : Acquired cellular immunity

North, 1978. J. Immunol. 121: 806.           (A quick biological/historical.

Cohn, 1978. J. Immunol. 121: 813.           (perspective

Nathan et al, 1993. J. Exp. Med. 158: 670. Ifng is MAF.

Dalton et al, 1993. Science 259: 1739.  Ifng  knock out.

Bach et al 1997. Ann. Rev. Immunol. 15: 563-91. Ifng  Receptors and signalling.

Kindler et al. 1989. Cell 56: 731. Role of TNF in granuloma formation.

Havell, 1987. J. Immunol. 139: 4225. TNF protective against Listeria.

Taylor et al 2001.  Current Op. Immunol. 13: 611-616.  Immunotherapy rheumatoid arthritis.

Vidal et al 1993. Cell 73: 439. Bcg gene (N-ramp). J. Exp. Med.1995. 182: 655 ko.

Trinchieri, Curr. Opin. in Immunol. 1997. 9: 17-23. Cytokines acting on or secreted by MØ during intracellular infection (IL-10, IL-12, Ifng).

Sutterwala et al.  1997. J.  Exp.  Med. 185: 1977-85.  Selective suppression of interleukin-12 induction after macrophage receptor ligation.

Michel & Feron 1997.  Nitric oxide synthase.  J.  Clin.  Invest.  100: 2146-2152.

Shiloh, Nathan et al 1999.  Immunity 10: 29-38.  Double ko phox and i-NOS.

Haworth et al 1997.  J.  Exp.  Med. 186: 1431-1439.  SR-A protects against shock.

Haziot et al 1996.  Immunity 4: 407-144. CD14 ko highly resistant to LPS shock.

Naka et al. 1999.  Trends in Bioch. Sci.  24: 394. SOCS.

Ehrt et al 2001.  J. Exp. Med. 194: 1123-1139.  MØ transcriptome (Ifng, Tb). NOS/Oxidase.

Lang et al. 2002.  J. Immunol. 169: 2253-63. IL-10 microarray.

 

Alternate Activation and Regulation

Stein et al, 1992. J. Exp. Med. 176: 287. IL-4 and Mannose Receptor.

Nathan et al, 1988. Nature 334: 260.  Tgfß deactivates respiratory burst.

Gordon 2002.  Nature Reviews (In Press). Review.

 

GENERAL REVIEWS

 

For general reviews written within the last few years:

 

Encyclopedia of Life Sciences:   http://www.els.net

 

 

_______________________________________________________________________________

 

 

S. GORDON                                F.H.S. IMMUNOLOGY                                              2003

 

QUESTIONS ON MACROPHAGES

 

 

1.     Assess our knowledge of macrophage differentiation in vivo  and in vitro.            

        How can the present confusion about lineage relationships (e.g. macrophages versus dendritic cells) be clarified?

 

2.     What contribution does the macrophage make to “non-self” recognition, compared with other cell types.

 

3.     Discuss the role of non-opsonic MØ plasma membrane receptors in the induction and regulation of immunity.

 

4.     Compare the mechanisms and significance of apoptotic cell clearance by macrophages and dendritic cells.

 

 5.     Is it reasonable to consider that the macrophage calls the tune in regard to Th 1/2               

        type differentiation?

        Would it be reasonable to classify activation of MØ as M1 (Th1) versus M2 (Th2)?

 

6.     How have 'classical' concepts of innate and acquired activation of macrophages fared more recently?

 

7.     Why do immunologists not take macrophages seriously? Argue the case for the opposing view.

 

8.     How well have our ideas about the immunobiology of macrophages fared in the light of gene knock-out experiments?

 

9.     Discuss the role of TNFa in cell-mediated immunity.  How can its production/activity be regulated therapeutically?

 

10.   Discuss the importance of tissue microenvironment in relation to MØ immunologic functions.

 

NB             Consult SG if you would like to arrange for tutorials on macrophage-related topics.