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Mast-cell responses to pathogens

Key Points

  • Mast cells have been most widely studied in the context of allergic disease, but they have been clearly shown to have a crucial role in host defence in vivo against several bacterial and parasitic infections.

  • Mast cells are found in large numbers at sites that are exposed to the external environment, such as the skin, airways and intestine, and are frequently located close to blood vessels and nerves. Residing in this location allows mast cells to have a sentinel role in early host defence.

  • Mast cells produce three main classes of mediator — pre-formed granule-associated mediators, lipid-derived mediators, and a wide variety of cytokines and chemokines — which allow mast cells to initiate and modify physiological responses and immune function.

  • Mast cells can selectively produce different classes of mediator and alternative profiles of cytokines and chemokines in response to specific pathogens and their products, thereby allowing the selective activation and recruitment of specific cell types, such as neutrophils, eosinophils, dendritic cells and T cells.

  • Mast cells express a wide range of direct and indirect receptors, which provide a mechanism for selective responses to pathogens. These include Toll-like receptors, Fc receptors and complement receptors.

  • Mast cells have an important role in initiating the recruitment of effector cells that are appropriate for fighting infection with different types of pathogen. This occurs through the selective production of mediators that can activate endothelial cells, increase vascular permeability and provide chemotactic signals to other immune-effector cells.

  • In addition to well-documented effects on innate immune function, mast-cell activity can also influence the acquired immune response, particularly through 'activation' of lymph nodes and interactions with dendritic cells.

  • The ability of mast cells to respond to pathogens, although important to host survival in some situations, might also have detrimental effects. Mast-cell responses to pathogens could contribute to the pathology of allergic disease and to other chronic inflammatory conditions.

Abstract

Mast cells have mainly been studied in the setting of allergic disease, but the importance of mast cells for host defence against several pathogens has now been well established. The location of mast cells, which are found closely associated with blood vessels, allows them to have a crucial sentinel role in host defence. The mast cell has a unique 'armamentarium' of receptor systems and mediators for responding to pathogen-associated signals. Studies of this intriguing immune-effector cell provide important insights into the complex mechanisms by which appropriate innate and acquired immune responses are initiated.

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Figure 1: The strategic location of mast cells.
Figure 2: Important ways in which mast cells are activated by pathogens.
Figure 3: Mechanisms by which mast cells enhance immune effector-cell recruitment.

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DATABASES

Entrez Gene

α2β1-integrin

C3aR

C5aR

CCL3

CCL4

CCL5

CCL11

CCL20

CD48

CR1

CR2

CR3

CR4

CRAMP

CXCL8

CXCL10

FcγRI

FcγRII

FcεRI

GM-CSF

IFN-γ

IL-1β

IL-3

IL-4

IL-5

IL-6

IL-10

IL-12

IL-13

IL-18

KIT

LL37

LTC4 synthase

PAR2

stem-cell factor

TLR1

TLR2

TLR3

TLR4

TLR5

TLR6

TLR7

TLR8

TLR9

TNF

transforming growth factor-β

FURTHER INFORMATION

Jean Marshall's laboratory

Glossary

POLYBASIC COMPOUNDS

Compounds that contain repeats of negatively charged units, such as compound 48/80 and magainin.

DISODIUM CROMOGLYCATE

A frequently used mast-cell stabilizing agent that prevents degranulation of certain types of mast cell in response to IgE-mediated activation.

ANGIOGENESIS

The development of new blood vessels from existing blood vessels. It is frequently associated with tumour development and inflammation.

BRONCHOCONSTRICTOR

An agent that induces constriction of airway smooth muscle and thereby reduces the capacity for air-flow in the main airways.

CC-CHEMOKINE

A member of the chemokine family in which the first two amino-terminal cysteine residues are adjacent.

CXC-CHEMOKINE

A member of the chemokine family in which the first two amino-terminal cysteine residues are separated by an intervening amino acid.

B-CELL SUPERANTIGENS

Substances that induce activation of some cells that express cell-surface immunoglobulin, through binding that is independent of the antigen specificity of the immunoglobulin.

CAECAL LIGATION AND PUNCTURE

An experimental model of peritonitis in rodents, in which the caecum is ligated and then punctured, thereby forming a small hole. This leads to leakage of intestinal bacteria into the peritoneal cavity and subsequent peritoneal infection.

DENGUE VIRUS

A member of the dengue group of RNA viruses that cause dengue fever.

ANTIBODY-ENHANCED INFECTION

A viral infection that is enhanced by the presence of subneutralizing concentrations of virus-specific antibody.

EXOSOMES

Small lipid-bilayer vesicles that are released from activated cells. They comprise either plasma membrane or membrane derived from intracellular vesicles.

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Marshall, J. Mast-cell responses to pathogens. Nat Rev Immunol 4, 787–799 (2004). https://doi.org/10.1038/nri1460

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