Innate Immunity Cell Identity Markers

Innate Immunity

Rapid responses to invading pathogens are mediated by the cells and humoral factors of the innate immune system. These responses are activated by the interaction between pathogen antigens and pattern recognition receptors (PRRs), localized to the surface or intracellular compartments of innate immune cells. This initial response is somewhat generic, as receptors are only able to recognize a limited repertoire of motifs from pathogen-derived molecules including lipopolysaccharides, lipoproteins and nucleic acids, collectively referred to as pathogen-associated molecular patterns (PAMPs).

Complement C3 expression in mouse kidney cells IHC

TLR3 expression in mouse colon IHC

Immunohistochemistry: Complement C3 Antibody (11H9) [NB200-540] - C3 protein fragments deposited on kidney cells of MPL-lpr mouse. Staining with antibody 11H9. Glomerular staining pattern. Fixation in 4% paraformaldehyde in PBS pH 7.4. Vibratome sections of 4 um. Pretreated with 3% hydrogen peroxide for 20 min to quench endogenous peroxidases. Microwaved in antigen unmasking solution for 2-5 minutes as antigen retrieval.

Immunohistochemistry-Paraffin: TLR3 Antibody (40C1285.6) [NBP2-24875] - Mouse colon using TLR3 antibody (clone 40C1285.6) at 1:500 dilution with HRP-DAB detection and hematoxylin counterstaining. Intense signal was found in subset of cells at the bases of the crypts.

In addition to PAMPs, innate immune cells respond to molecular patterns associated with tissue injury or damage-associated molecular patterns (DAMPs). These are cell-derived molecules induced by stress or injury which may be released even in the absence of infection. Both PAMPs and DAMPs engage innate cellular mediators, including cytotoxic and phagocytic cells via interaction with Toll-like (TLRs), NOD-like, RIG-I-like and AIM2-like receptors. Soluble mediators of the innate response include cytokines, complement and acute phase proteins.

Explore Toll-Like Receptor Signaling

Innate cellular mediators: functions and markers

Cell Type Function Markers

Dendritic cells

Dendritic cell

Antigen presenting cells, reside in peripheral tissues where they sequester and process antigens for presentation to lymphocytes. Dendritic cells may be classified into three subsets:Myeloid- CD11c, CD13, CD33, CD11b; Plasmacytoid- CD123, CD303, and CD304; Monocyte-related- CD14, all of which have high expression of MHCII (HLA-DR). 

CD11c, CLIP-170, Fascin, MADDAM, NLDC-145, MHCII (HLA-DR), CD33, CD123, CD16, CD128b

Activation: CD83, CD80, CD86, CD40, MHCII (HLA-DR)

Macrophages (and Monocytes)


Phagocytic cells, participate in both innate and adaptive immunity, in the capture of pathogens and as antigen presenting cells. Macrophages persist and monitor tissue for prolonged periods where they demonstrate distinct tissue-specific phenotypes and origins. While some macrophages are yolk sac-derived, others differentiate from bone marrow-derived monocytes. Based on recent nomenclature, macrophages may be classified into two main subsets: M1 classically activated and M2 alternatively activated macrophages, although more subpopulations continue to be identified. 

CD68, CD64, CSF-1R, F4-80 (mice), CD11b

Activation: M1 classically activated- CD68, CD80, CD86, CD38, CD11c

M2 alternatively activated- CD68, CD163, MMR/CD206, MGL1 , MGL2, Egr2

Monocytes: CD14, CD16, CD115 (mice), Ly-6C (mice)

Mast cells

Mast Cells

Mature mast cells are found in association with a variety of tissues including those with high environmental influence (e.g., mucosal and skin tissues). Mast cells degranulate following stimulation through IgE-dependent and independent mechanisms and release several products including proteases, TNF-alpha, GM-CSF and cytokines.

CD34 (mice), Chymase, CD117/c-kit, Fc epsilon RI

Activation: LAMP-I (CD1-7a), LAMP-2 (CD107b)

Natural killer cells (NK)

Natural killer cells

NK cells recognize infected or transformed cells and target them for lysis via the release of perforins and granzymes. Activated NK cells secrete various cytokines including IL-1, IL-2 and INF-gamma. Two main subsets are identifiable for their differential expression of CD16 and CD56.

CD56, CD16, CD57, CD161, NKp46, NKp30, CD25

Activation: CD69, CD107a, NKp46, NKp30, CD95


Neutrophils Neutrophils

Basophils Basophils

Eosinophils Eosinophils

Phagocytic cells with short life span (days) characterized by the presence of cytosolic granules containing a variety of immunologically active substances which are microbicidal, cytotoxic, or inflammatory.

Neutrophils: CD16, CD11b, CD16b, CD66c, CD66b, Ly-6G/Gr-1 (mice)

Basophils: CD49b (mice), CD41 (mice), Fc epsilon RI, CD203c, CD123 , CCR3/CD193

Eosinophils: CD11b, CCR3/CD193, F4/80 (mice), Siglec-F (mice), EMR1, Siglec-8


Neutrophil: CD11b, CD88, CD18, L-selectin (CD62L), CD32, CD54, CD66b

Basophil: CD41 (mice), CD200R, CD63, CD203c, CD69, CD13, CD164, CD107a, CRTH2/DP2

Eosinophils: CD69, CD63, CD44

Learn about NK cells in anti-cancer therapy

Flow cytometry analysis of B7-2/CD86 expression in Human Ramos lymphoma cell line

Human Ramos lymphoma cell line was stained with: A. Mouse Anti-Human B7-2/CD86 Monoclonal Antibody (Catalog # MAB141, filled histogram) or isotype control antibody (Catalog # MAB002, open histogram) followed by PE-conjugated Goat Anti-Mouse IgG secondary antibody (Catalog # F0102B); B. B7-2/CD86 knockout Ramos human lymphoma cell line was stained with Mouse Anti-Human B7-2/CD86 Monoclonal Antibody (Catalog #MAB141, filled histogram) or isotype control antibody (Catalog #MAB002, open histogram) followed by PE-conjugated Goat anti-Mouse IgG Secondary Antibody (Catalog #F0102B). No staining in the B7-2/CD86 knockout Ramos cell line was observed. View our protocol for Staining Membrane-associated Proteins.

CD11b expression in mouse spleen IHCImmunocytochemistry/Immunofluorescence: CD11b Antibody (M1/70.15) [NB600-1327] - ICC/IF analysis of RAW264.7 cells using CD11b antibody (clone M1/70.15) with Dylight 488 conjugated secondary (green). Nuclei and tubulin were stained with DAPI (blue) and Dylight 550 (red).

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Select References

Amano, H., Amano, E., Santiago-Raber, M. L., Moll, T., Martinez-Soria, E., Fossati-Jimack, L., … Izui, S. (2005). Selective expansion of a monocyte subset expressing the CD11c dendritic cell marker in the Yaa model of systemic lupus erythematosus. Arthritis and Rheumatism.

Baaten, B. J., Li, C. R., & Bradley, L. M. (2010). Multifaceted regulation of T cells by CD44. Communicative & integrative biology, 3(6), 508-12. doi:  [10.4161/cib.3.6.13495]

Boumiza, R., Debard, A. L., & Monneret, G. (2005). The basophil activation test by flow cytometry: Recent developments in clinical studies, standardization and emerging perspectives. Clinical and Molecular Allergy.

Breel, M., Laman, J., & Kraal, G. (1988). Murine Hybrid Cell Lines Expressing the NLDC-145 Dendritic Cell Determinant. Immunobiology.

Chávez-Galán, L., Olleros, M. L., Vesin, D., & Garcia, I. (2015). Much more than M1 and M2 macrophages, there are also CD169+and TCR+macrophages. Frontiers in Immunology.

Collin, M., Mcgovern, N., & Haniffa, M. (2013). Human dendritic cell subsets. Immunology.

De Clerck, L. S., De Gendt, C. M., Bridts, C. H., Van Osselaer, N., & Stevens, W. J. (1995). Expression of neutrophil activation markers and neutrophil adhesion to chondrocytes in rheumatoid arthritis patients: relationship with disease activity. Research in Immunology.

Drew, E., Merkens, H., Chelliah, S., Doyonnas, R., & McNagny, K. M. (2002). CD34 is a specific marker of mature murine mast cells. Experimental Hematology.

Ehrnsperger, A., Rehli, M., Thu-Hang, P., & Kreutz, M. (2005). Epigenetic regulation of the dendritic cell-marker gene ADAM19. Biochemical and Biophysical Research Communications.

Fortunati, E., Kazemier, K. M., Grutters, J. C., Koenderman, L., & Van Den Bosch, V. J. M. M. (2009). Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease. Clinical and Experimental Immunology.

Grützkau, A., Smorodchenko, A., Lippert, U., Kirchhof, L., Artuc, M., & Henz, B. M. (2004). LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for activation-induced secretion of human mast cells. Cytometry Part A.

Haldar, M., & Murphy, K. M. (2014). Origin, development, and homeostasis of tissue-resident macrophages. Immunological reviews, 262(1), 25-35. doi: 10.1111/imr.12215

Hellman, P., & Eriksson, H. (2007). Early Activation Markers of Human Peripheral Dendritic Cells. Human Immunology.

Jablonski, K. A., Amici, S. A., Webb, L. M., Ruiz-Rosado, J. D. D., Popovich, P. G., Partida-Sanchez, S., & Guerau-De-arellano, M. (2015). Novel markers to delineate murine M1 and M2 macrophages. PLoS ONE.

Lakschevitz, F. S., Hassanpour, S., Rubin, A., Fine, N., Sun, C., & Glogauer, M. (2016). Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Experimental Cell Research.

Mahanonda, R., Sa-Ard-Iam, N., Yongvanitchit, K., Wisetchang, M., Ishikawa, I., Nagasawa, T., … Pichyangkul, S. (2002). Upregulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal disease. Journal of Periodontal Research.

Mahnke, K., Becher, E., Ricciardi-Castagnoli, P., Luger, T. A., Schwarz, T., & Grabbe, S. (1997). CD14 is expressed by subsets of murine dendritic cells and upregulated by lipopolysaccharide. Adv Exp Med Biol.

Matsumoto, K., Appiah-Pippim, J., Schleimer, R. P., Bickel, C. A., Beck, L. A., & Bochner, B. S. (1998). CD44 and CD69 represent different types of cell-surface activation markers for human eosinophils. American Journal of Respiratory Cell and Molecular Biology.

McLennan, I. S. (1993). Resident macrophages (ED2- and ED3-positive) do not phagocytose degenerating rat skeletal muscle fibres. Cell & Tissue Research.

Nishikawa, K., Morii, T., Ako, H., Hamada, K., Saito, S., & Narita, N. (1992). In vivo expression of CD69 on lung eosinophils in eosinophilic pneumonia: CD69 as a possible activation marker for eosinophils. The Journal of Allergy and Clinical Immunology.

Piccioli, D., Tavarini, S., Borgogni, E., Steri, V., Nuti, S., Sammicheli, C., … Wack, A. (2007). Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets. Blood.

Pinkus, G. S., Lones, M. A., Matsumura, F., Yamashiro, S., Said, J. W., & Pinkus, J. L. (2002). Langerhans cell histiocytosis: Immunohistochemical expression of fascin, a dendritic cell marker. American Journal of Clinical Pathology.

Sahashi, K., Ibi, T., & Zhang, G. (1997). Immunohistochemical localization of chymase; a mast cell marker and clinical significance in diseased human skeletal muscle. Clinical Neurology.

Sahin, U., Neumann, F., Türeci, Ö., Schmits, R., Perez, F., & Pfreundschuh, M. (2002). Hodgkin and Reed-Sternberg cell–associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells. Blood, 100(12), 4139-4145. Accessed November 30, 2018.

Tang, D., Kang, R., Coyne, C. B., Zeh, H. J., & Lotze, M. T. (2012). PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunological reviews, 249(1), 158-75. doi:  [10.1111/j.1600-065X.2012.01146.x]

Yoshimura, C., Yamaguchi, M., Iikura, M., Izumi, S., Kudo, K., Nagase, H., … Hirai, K. (2002). Activation markers of human basophils: CD69 expression is strongly and preferentially induced by IL-3. Journal of Allergy and Clinical Immunology.