Introduction: Macrophages are among the oldest cell types in the animal kingdom, and they have a long evolutionary history and experience various evolutionary pressures. It was clear from the earliest studies that variations exist in macrophage populations. Macrophages are known to adapt to their microenvironment. Although the paradigm for macrophage plasticity is their flexible program driven by environmental signals, the most common working hypothesis is that of a dichotomy between two major macrophage phenotypes, M1 and M2. Methods: A PubMed and Web of Science databases search was performed providing evidences that numerous authors have expanded the concept of plasticity and conducted experimental studies focusing on the complex program of phenotypes. Results and Conclusions: This review evaluated a number of issues relating to macrophage plasticity, environmental heterogeneity and the potential for changes to be reversal or non reversal in an ecological context. The ecological principles of phenotypic plasticity which can assist in evaluating and interpreting macrophage experimental data are discussed as well. © 2013 Springer Basel.629835843Ottaviani, E., Franceschi, C., The invertebrate phagocytic immunocyte: Clues to a common evolution of immune and neuroendocrine systems (1997) Immunol Today., 18, pp. 169-174. , 9136453 10.1016/S0167-5699(97)84663-4 1:CAS:528:DyaK2sXktFWmtb8%3DOttaviani, E., Malagoli, D., Grimaldi, A., De Eguileor, M., The case of the "serfdom" condition of phagocytic immune cells (2012) Invert Surv J., 9, pp. 134-138Desjardins, M., Houde, M., Gagnon, E., Phagocytosis: The convoluted way from nutrition to adaptaive immunity (2005) Immunol Rev., 207, pp. 158-165. , 16181334 10.1111/j.0105-2896.2005.00319.x 1:CAS:528:DC%2BD2MXhtFOqtL7FAderem, A., Underhill, D.M., Mechanisms of phagocytosis in macrophages (1999) Annu Rev Immunol., 17, pp. 593-623. , 10358769 10.1146/annurev.immunol.17.1.593 1:CAS:528:DyaK1MXjtVWmtrg%3DDale, D.C., Boxer, L., Liles, W.C., The phagocytes: Neutrophils and monocytes (2008) Blood, 112, pp. 935-945. , 18684880 10.1182/blood-2007-12-077917 1:CAS:528:DC%2BD1cXpvVOks7s%3DMetchnikoff, E., (1893) Lectures on the Comparative Pathology of Inflammation, , Trench LondonSilverstein, A.M., (1989) A History of Immunology, pp. 40-56. , Academic San DiegoHume, D.A., Ross, I.L., Himes, S.R., Sasmono, R.T., Wells, C.A., Ravasi, T., The mononuclear phagocyte system revisited (2002) J Leukoc Biol., 72, pp. 621-627. , 12377929 1:CAS:528:DC%2BD38XotFShsLs%3DHabicht, G.S., Primordial immunity: Foundations for the vertebrate immune system (1994) The Vertebrate Immune System, pp. ix-xi. , Beck C, Habicht GS, Cooper EL, Marchalonis JJ, editors New York: New York Academy of SciencesMaurya, M.R., Benner, C., Pradervand, S., Glass, C., Subramaniam, S., Systems biology of macrophages (2007) Adv Exp Med Biol., 598, pp. 62-79. , 17892205 10.1007/978-0-387-71767-8-6Germain, R.N., Meier-Schellersheim, M., Nita-Lazar, A., Fraser, I.D., Systems biology in immunology: A computational modeling perspective (2011) Annu Rev Immunol., 29, pp. 527-585. , 21219182 10.1146/annurev-immunol-030409-101317 1:CAS:528: DC%2BC3MXltlKnsLo%3DMurray, P.J., Wynn, T.A., Protective and pathogenic functions of macrophage subsets (2011) Nat Rev Immunol., 11, pp. 723-737. , 21997792 10.1038/nri3073 1:CAS:528:DC%2BC3MXhtlWltb%2FEHalmilton, J.A., Therapeutic potential of targeting inflammation (2013) Inflamm Res., 62, pp. 653-665. , 10.1007/s00011-013-0614-3Gordon, S., Martinez, F.O., Alternative activation of macrophages: Mechanism and functions (2010) Immunity, 32, pp. 593-604. , 20510870 10.1016/j.immuni.2010.05.007 1:CAS:528:DC%2BC3cXnt1Kls78%3DMartinez, F.O., Helming, L., Gordon, S., Alternative activation of macrophages: An immunologic functional perspective (2009) Annu Rev Immunol., 27, pp. 451-483. , 19105661 10.1146/annurev.immunol.021908.132532 1:CAS:528: DC%2BD1MXlsFSltrk%3DStout, R.D., Watkins, S.K., Suttles, J., Functional plasticity of macrophages: In situ reprogramming of tumor-associated macrophages (2009) J Leukoc Biol., 86, pp. 1105-1109. , 19605698 10.1189/jlb.0209073 1:CAS:528:DC%2BD1MXhtlyjs7jNMosser, D.M., Edwards, J.P., Exploring the full spectrum of macrophage activation (2008) Nat Rev Immunol., 8, pp. 958-969. , 19029990 10.1038/nri2448 1:CAS:528:DC%2BD1cXhsVWlsLfIGalli, S.J., Borregaard, N., Wynn, T.A., Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils (2011) Nat Immunol., 12, pp. 1035-1044. , 22012443 10.1038/ni.2109 1:CAS:528:DC%2BC3MXhtlChtrnEWeidenbusch, M., Anders, H.-J., Tissue microenvironments define and get reinforced by macrophage phenotypes in homeostasis or during inflammation, repair and fibrosis (2012) J Innate Immun., 4, pp. 463-477. , 22507825 10.1159/000336717 1:CAS:528:DC%2BC38Xht12mtrfJHamilton, T.A., Molecular basis of macrophage activation: From gene expression to phenotypic diversity (2002) The Macrophage, pp. 74-102. , B. Burke C.E. Lewis (eds) Oxford University Press New YorkGrage-Griebenow, E., Flad, H.D., Ernst, M., Heterogeneity of human peripheral blood monocyte subsets (2001) J Leukoc Biol., 69, pp. 11-20. , 11200054 1:CAS:528:DC%2BD3MXlvFCisA%3D%3DErwig, L.P., Kluth, D.C., Rees, A.J., Macrophage heterogeneity in renal inflammation (2003) Nephrol Dial Transplant., 18, pp. 1962-1965. , 13679464 10.1093/ndt/gfg313Gordon, S., Taylor, P.R., Monocyte and macrophage heterogeneity (2005) Nat Rev Immunol., 5, pp. 953-964. , 16322748 10.1038/nri1733 1:CAS:528:DC%2BD2MXht1Kntr3NKono, H., Fujii, H., Asakawa, M., Yamamoto, M., Maki, A., Matsuda, M., Functional heterogeneity of the Kupffer cell population is involved in the mechanism of gadolinium chloride in rats administered endotoxin (2002) J Surg Res., 106, pp. 179-187. , 12127824 10.1006/jsre.2002.6434 1:CAS:528:DC%2BD38XltlKgsr0%3DHe, Y., Sadahiro, T., Noh, S.I., Wang, H., Todo, T., Chai, N.N., Flow cytometric isolation and phenotypic characterization of two subsets of ED2(+) (CD163) hepatic macrophages in rats (2009) Hepatol Res., 39, pp. 1208-1218. , 19624775 10.1111/j.1872-034X.2009.00528.x 1:CAS:528:DC%2BC3cXot1Kjur4%3DKinoshita, M., Uchida, T., Sato, A., Nakashima, M., Nakashima, H., Shono, S., Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice (2010) J Hepatol., 53, pp. 903-910. , 20739085 10.1016/j.jhep.2010.04.037 1:CAS:528:DC%2BC3cXht1Cmu77IMovita, D., Kreefft, K., Biesta, P., Van Oudenaren, A., Leenen, P.J., Janssen, H.L., Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages (2012) J Leukoc Biol., 92, pp. 723-733. , 22685319 10.1189/jlb.1111566 1:CAS:528:DC%2BC38XhsFSmtrrFKraal, G., Cells in the marginal zone of the spleen (1992) Int Rev Cytol., 132, pp. 31-74. , 1555921 10.1016/S0074-7696(08)62453-5 1:STN:280:DyaK383htVamtQ%3D%3DDen Haan, J.M., Kraal, G., Innate immune functions of macrophage subpopulations in the spleen (2012) J Innate Immun., 4, pp. 437-445. , 10.1159/000335216Gordon, S., Innate immune functions of macrophages in different tissue environments (2012) J Innate Immun., 4, pp. 409-410. , 22699934 10.1159/000339280Taylor, P.R., Martinez-Pomares, L., Stacey, M., Lin, H.H., Brown, G.D., Gordon, S., Macrophage receptors and immune recognition (2005) Annu Rev Immunol., 23, pp. 901-944. , 15771589 10.1146/annurev.immunol.23.021704.115816 1:CAS:528: DC%2BD2MXktFOju7Y%3DLiddiard, K., Rosas, M., Davies, L.C., Jones, S.A., Taylor, P.R., Macrophage heterogeneity and acute inflammation (2011) Eur J Immunol., 41, pp. 2503-2508. , 21952806 10.1002/eji.201141743 1:CAS:528:DC%2BC3MXhtVOktbbPHashimoto, D., Miller, J., Merad, M., Dendritic cell and macrophage heterogeneity in vivo (2011) Immunity, 35, pp. 323-335. , 21943488 10.1016/j.immuni.2011.09.007 1:CAS:528:DC%2BC3MXht1WmurrNRutherford, M.S., Witsel, A., Schook, L.B., Mechanisms generating functionally heterogeneous macrophages: Chaos revisited (1993) J Leukoc Biol., 53, pp. 602-618. , 8501399 1:CAS:528:DyaK3sXlsFOktbg%3DSchust, D.J., Magamatsu, T., Does the classical M1/M2 dichotomy reflect the functional phenotypes of human decidual macrophages? (2011) Expert Rev Obstr Gynecol., 4, pp. 377-380. , 10.1586/eog.11.34Porcheray, F., Viaud, S., Rimaniol, A.C., Léone, C., Samah, B., Dereuddre-Bosquet, N., Macrophage activation switching: An asset for the resolution of inflammation (2005) Clin Exp Immunol., 142, pp. 481-489. , 16297160 1:CAS:528:DC%2BD2MXhtlWqtrrPMantovani, A., Macrophage diversity and polarization: In vivo veritas (2006) Blood, 108, pp. 408-409. , 10.1182/blood-2006-05-019430 1:CAS:528:DC%2BD28XntFehsbk%3DBiswas, S.K., Chittezhath, M., Shalova, I.N., Lim, J.Y., Macrophage polarization and plasticity in health and disease (2012) Immunol Res., 53, pp. 11-24. , 22418728 10.1007/s12026-012-8291-9 1:CAS:528:DC%2BC38XhtVGhtbrODaley, J.M., Reichner, J.S., Mahoney, E.J., Manfield, L., Henry, Jr.W.L., Mastrofrancesco, B., Modulation of macrophage phenotype by soluble product(s) released from neutrophils (2005) J Immunol., 174, pp. 2265-2272. , 15699161 1:CAS:528:DC%2BD2MXhtV2rt74%3DAdamson, S., Leitinger, N., Phenotypic modulation of macrophages in response to plaque lipids (2011) Curr Opin Lipidol., 22, pp. 335-342. , 21841486 10.1097/MOL.0b013e32834a97e4 1:CAS:528:DC%2BC3MXhtFClsLjJGleissner, C.A., Macrophage phenotype modulation by CXCL4 in atherosclerosis (2012) Front Physiol., 3, p. 1. , 22275902 10.3389/fphys.2012.00001 1:CAS:528:DC%2BC38Xis12ns74%3DGratchev, A., Schledzewski, K., Guillot, P., Goerdt, S., Alternatively activated antigen-presenting cells: Molecular repertoire, immune regulation, and healing (2001) Skin Pharmacol Appl Skin Physiol., 14, pp. 272-279. , 11586068 10.1159/000056357 1:CAS:528:DC%2BD3MXntlemtL8%3DMantovani, A., Sozzani, S., Locati, M., Allavena, P., Sica, A., Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes (2002) Trends Immunol., 23, pp. 549-555. , 12401408 10.1016/S1471-4906(02)02302-5 1:CAS:528:DC%2BD38XotVKktrc%3DStein, B.E., Burr, D., Constantinidis, C., Laurienti, P.J., Alex, M.M., Perrault, T.J., Semantic confusion regarding the development of multisensory integration: A practical solution (2010) Eur J Neurosci., 31, pp. 1713-1720. , 20584174 10.1111/j.1460-9568.2010.07206.xHuang, H., Fletcher, A., Niu, Y., Wang, T.Y., Yu, L., Characterization of lipopolysaccharide-stimulated cytokine expression in macrophages and monocytes (2012) Inflamm Res., 61, pp. 1329-1338. , 22842767 10.1007/s00011-012-0533-8 1:CAS:528:DC%2BC38Xhs1Ogt7vJZhangw, X., Xiong, S., Blockade of Notch1 signaling alleviates murine lupus via blunting macrophage activation and M2b polarization (2010) J Immunol., 184, pp. 6465-6478. , 10.4049/jimmunol.0904016Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., Locati, M., The chemokine system in diverse forms of macrophage activation and polarization (2004) Trends Immunol., 25, pp. 677-686. , 15530839 10.1016/j.it.2004.09.015 1:CAS:528:DC%2BD2cXptl2ktbs%3DStout, R.D., Jiang, C., Matta, B., Tietzel, I., Watkins, S.K., Suttles, J., Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences (2005) J Immunol., 175, pp. 342-349. , 15972667 1:CAS:528:DC%2BD2MXltlynu70%3DStout, R.D., Suttles, J., Functional plasticity of macrophages: Reversible adaptation to changing microenvironments (2004) J Leukoc Biol., 76, pp. 509-513. , 15218057 10.1189/jlb.0504272 1:CAS:528:DC%2BD2cXnsVaksrg%3DStout, R.D., Suttles, J., Immunosenescence and macrophage functional plasticity: Dysregulation of macrophage function by age-associated microenvironmental changes (2005) Immunol Rev., 205, pp. 60-71. , 15882345 10.1111/j.0105-2896.2005.00260.x 1:CAS:528:DC%2BD2MXmtl2ju7Y%3DStout, R.D., Macrophage functional phenotypes: No alternatives in dermal wound healing? (2010) J Leukoc Biol., 87, pp. 19-21. , 20047887 10.1189/jlb.0509311 1:CAS:528:DC%2BC3cXit1Wqsw%3D%3DMills, C.D., Kincaid, K., Alt, J.M., Heilman, M.J., Hill, A.M., M-1/M-2 macrophages and the Th1/Th2 paradigm (2000) J Immunol., 164, pp. 6166-6173. , 10843666 1:CAS:528:DC%2BD3cXktFWlsbw%3DMeyer, M., Huaux, F., Gavilanes, X., Van Den Brûle, S., Lebecque, P., Lore, S., Azithromycin reduces exaggerated cytokine production by M1 alveolar macrophages in cystic fibrosis (2009) Am J Respir Cell Mol Biol., 41, pp. 590-602. , 19244203 10.1165/rcmb.2008-0155OC 1:CAS:528:DC%2BD1MXhtlCktbzLOrtega, M.T., Xie, L., Mora, S., Chapes, S.K., Evaluation of macrophage plasticity in brown and white adipose tissue (2011) Cell Immunol., 271, pp. 124-133. , 21757190 10.1016/j.cellimm.2011.06.012Empey, K.M., Orend, J.G., Peebles, Jr.R.S., Egaña, L., Norris, K.A., Oury, T.D., Stimulation of immature lung macrophages with intranasal interferon gamma in a novel neonatal mouse model of respiratory syncytial virus infection (2012) PLoS ONE., 7, p. 40499. , 22792355 10.1371/journal.pone.0040499 1:CAS:528:DC%2BC38XhtVemsrzLColhone, M.C., Arrais-Silva, W.W., Picolli, C., Giorgio, S., Effect of hypoxia on macrophage infection by Leishmania amazonensis (2004) J Parasitol., 90, pp. 510-515. , 15270094 10.1645/GE-3286Degrosolli, A., Colhone, M.C., Arrais-Silva, W.W., Giorgio, S., Hypoxia modulates expression of the 70-kD heat shock protein and reduces Leishmania infection in macrophages (2004) J Biomed Sci., 11, pp. 847-854Degrossoli, A., Bosetto, M.C., Lima, C.B., Giorgio, S., Expression of hypoxia-inducible factor 1α in mononuclear phagocytes infected with Leishmania amazonensis (2007) Immunol Lett., 114, pp. 119-125. , 17983667 10.1016/j.imlet.2007.09.009 1:CAS:528:DC%2BD2sXhtlyksr7ODegrossoli, A., Arrais-Silva, W.W., Colhone, M.C., Gadelha, F.R., Joazeiro, P.J., Giorgio, S., The influence of low oxygen on macrophage response to Leishmania infection (2011) Scand J Immunol, 74, pp. 165-175. , 21517930 10.1111/j.1365-3083.2011.02566.x 1:CAS:528:DC%2BC3MXhtV2rurfLMurdoch, C., Giannoudis, A., Lewis, C.E., Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues (2004) Blood, 104, pp. 2224-2234. , 15231578 10.1182/blood-2004-03-1109 1:CAS:528:DC%2BD2cXovVegsbs%3DRahat, M.A., Bitterman, H., Lahat, N., Molecular mechanisms regulating macrophage response to hypoxia (2011) Front Immunol., 2, p. 45. , 22566835 10.3389/fimmu.2011.00045Bosco, M.C., Puppo, M., Blengio, F., Fraone, T., Cappello, P., Giovarelli, M., Monocytes and dendritic cells in a hypoxic environment: Spotlights on chemotaxis and migration (2008) Immunobiology, 213, pp. 733-749. , 18926289 10.1016/j.imbio.2008.07.031 1:CAS:528:DC%2BD1cXhtlCgt7%2FNMurdoch, C., Muthana, M., Lewis, C.E., Hypoxia regulates macrophage functions in inflammation (2005) J Immunol., 175, pp. 6257-6263. , 16272275 1:CAS:528:DC%2BD2MXhtF2jtbfMLahat, N., Rahat, M.A., Ballan, M., Weiss-Cerem, L., Engelmayer, M., Bitterman, H., Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-alpha secretion (2003) J Leukoc Biol., 74, pp. 197-205. , 12885936 10.1189/jlb.0303105 1:CAS:528:DC%2BD3sXmt1Ggur4%3DSpear, W., Chan, D., Coppens, I., Johnson, R.S., Giaccia, A., Blader, I.J., The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels (2006) Cell Microbiol., 8, pp. 339-352. , 16441443 10.1111/j.1462-5822.2005.00628.x 1:CAS:528:DC%2BD28XhsFantLo%3DNickel, D., Busch, M., Mayer, D., Hagemann, B., Knoll, V., Stenger, S., Hypoxia triggers the expression of human β defensin 2 and antimicrobial activity against Mycobacterium tuberculosis in human macrophages (2012) J Immunol., 188, pp. 4001-4007. , 22427634 10.4049/jimmunol.1100976 1:CAS:528:DC%2BC38XltFKgt7k%3DPuppo, M., Bosco, M.C., Federico, M., Pastorino, S., Varesio, L., Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages (2007) J Leukoc Biol., 81, pp. 528-538. , 17062606 10.1189/jlb.0506361 1:CAS:528:DC%2BD2sXhs1Wkt7g%3DDegrossoli, A., Giorgio, S., Functional alterations in macrophages after hypoxia selection (2007) Exp Biol Med., 232, pp. 88-95. , 1:CAS:528:DC%2BD2sXmslejsQ%3D%3DLeroux, A., Ferrere, G., Godie, V., Cailleux, F., Cailleux, F., Renoud, M.L., Gaudin, F., Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis (2012) J Hepatol., 57, pp. 141-149. , 22425624 10.1016/j.jhep.2012.02.028 1:CAS:528:DC%2BC38XovV2gu7g%3DLorne, E., Zmijewski, J.W., Zhao, X., Liu, G., Tsuruta, Y., Park, Y.-J., Dupont, H., Abraham, E., Role of extracellular superoxide in neutrophil activation: Interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production (2008) Am J Physiol Cell Physiol., 294, pp. 985-C993. , 18287332 10.1152/ajpcell.00454.2007 1:CAS:528:DC%2BD1cXkslOkt7s%3DNicholas, S.A., Coughlan, K., Yasinska, I., Lall, G.S., Gibbs, B.F., Calzolai, L., Sumbayev, V.V., Dysfunctional mitochondria contain endogenous high-affinity human Toll-like receptor 4 (TLR4) ligands and induce TLR4-mediated inflammatory reactions (2011) Int J Biochem Cell Biol., 43, pp. 674-681. , 21262374 10.1016/j.biocel.2011.01.012 1:CAS:528:DC%2BC3MXisFGmurw%3DRomagnoli, M., Gomez-Cabrera, M.C., Perrelli, M.G., Biasi, F., Pallardó, F.V., Sastre, J., Poli, G., Viña, J., Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type i diabetic rats (2010) Free Radic Biol Med., 49, pp. 171-177. , 20362663 10.1016/j.freeradbiomed.2010.03.024 1:CAS:528: DC%2BC3cXntVOnt78%3DLewis, C.L., Pollard, J.W., Distincts roles of macrophages in different tumor microenvironments (2006) Cancer Res, pp. 605-612Pettersen, J.S., Fuentes-Duculan, J., Suárez-Fariñas, M., Pierson, K.C., Pitts-Kiefer, A., Fan, L., Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated (2011) J Invest Dermatol., 131, pp. 1322-1330. , 21307877 10.1038/jid.2011.9 1:CAS:528:DC%2BC3MXmtV2jt74%3DStofanko, M., Kwon, S.Y., Badenhorst, P., Lineage tracing of lamellocytes demonstrates Drosophila macrophage plasticity (2010) PLoS ONE., 5, p. 14051. , 21124962 10.1371/journal.pone.0014051Dewitt, T.J., Scheiner, S.M., (2004) Phenotypic Plasticity. Functional and Conceptual Approaches, , Oxford University Press New YorkPigliucci, M., (2001) Phenotypic Plasticity: Beyond Nature and Nurture, , University Press BaltimoreSchlichting, C.D., Pigliucci, M., (1998) Phenotypic Evolution: A Reaction Norm Perspective, , Sinauer SunderlandChevin, L.M., Lande, R., Mace, G.M., Adaptation, plasticity, and extinction in a hanging environment: Towards a predictive theory (2010) PLos Biol, pp. e1000357Svennungsen, T.O., Holen Ø, Leimar, O., Inducible defenses: Continuous reaction norms or threshold traits? (2011) Am Nat., 178, pp. 397-410. , 21828995 10.1086/661250Fuller, T., The integrative biology of phenotypic plasticity (2003) Biol Philos., 18, pp. 381-389. , 10.1023/A:1023948505327Stearns, S.C., The evolutionary significance of phenotypic plasticity (1989) Bioscience, 39, pp. 436-445. , 10.2307/1311135Dodson, S., Predator-induced reaction norms (1989) Bioscience, 39, pp. 447-451. , 10.2307/1311136Ebert, D., A genome for the environment (2011) Science, 331, pp. 539-540. , 21292957 10.1126/science.1202092 1:CAS:528:DC%2BC3MXisFOmt7Y%3DDaley, J.M., Brancato, S.K., Thomay, A.A., Reichner, J.S., Albina, J.E., The phenotype of murine wound macrophages (2010) J Leukoc Biol., 87, pp. 59-67. , 20052800 10.1189/jlb.0409236 1:CAS:528:DC%2BC3cXit1WqtQ%3D%3DXu, W., Zhao, X., Daha, M.R., Reversible differentiation of pro- and anti-inflammatory macrophages (2013) Mol Immunol., 53, pp. 179-186. , 22944456 10.1016/j.molimm.2012.07.005 1:CAS:528:DC%2BC38XhsVKksrfMPiersma, T., Van Gils, J.A., (2011) The Flexible Phenotype. A Body-centred Integration of Ecology, Physiology, and Behavior, , New York: Oxford University PressWhitman, D.W., Agrawal, A.A., What is phenotypic plasticity and why is it important? (2009) Phenotypic Plasticity of Insects: Mechanisms and Consequences, pp. 1-63. , D.W. Whitman T.N. Ananthakrishnan (eds) Science Publishers Enfield 10.1201/b10201Lof, M.E., Reed, T.E., McNamara, J.M., Visser, M.E., Timing in a fluctuating environment: Environmental variability and asymmetric fitness curves can lead to adaptively mismatched avian reproduction (2012) Proc Biol Sci., 279, pp. 3161-3169. , 22628472 10.1098/rspb.2012.0431Jenkins, S.J., Ruckerl, D., Cook, P.C., Jones, L.H., Finkelman, F.D., Van Rooijen, N., Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation (2011) Science, 332, pp. 1284-1288. , 21566158 10.1126/science.1204351 1:CAS:528:DC%2BC3MXntVGltb4%3D