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The Macrophage as Therapeutic Target pp 409–457Cite as

Macrophage Immunity and Mycobacterium tuberculosis

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 158))

Abstract

Tuberculosis (TB) is rivalled only by the acquired immunodeficiency syndrome (AIDS) as a communicable cause of death. Yet of an estimated 2 billion individuals who have been infected with the pathogen Mycobacterium tuberculosis (Mtb), less than 10% will develop disease. For the remainder, natural immunity appears sufficient to limit bacterial growth. An integral component of host protection to TB is the activated macrophage. Mtb recognition, phagocytosis, vacuolar trafficking and redox-based killing are all enlisted as part of this cell’s anti-tubercular arsenal. When assembled together with lymphocytes and stromal elements as part of the tuberculoid granuloma, macrophages also provide a physical constraint to further dissemination. The liaison between macrophages and T cells in particular forms much of the current basis of vaccination in immunologically naive subjects. Recent experimentation with post-exposure vaccines, however, suggests that cellular immunity may not be fully elicited by the existing single-dose regimen. New approaches that embrace small molecule chemistry to enhance or mimic macrophage effector mechanisms, or which sensitise Mtb to further immunologic insult, could help address this issue. Harnessing the macrophage as a therapeutic target could thus prove a useful adjunct to TB vaccination and chemotherapy in the future.

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Abbreviations

AFB :

Acid-fast bacilli

AM:

Alveolar macrophage

BAL:

Bronchoalveolar lavage

CGD:

Chronic granulomatous disease

CR:

Complement receptor

FcR:

Fc receptor

GPI:

Glycosyl phosphatidylinositol

GTPase:

Guanosine 5′-triphosphatase

IFN-γ :

Interferon gamma

IL:

Interleukin

RF :

Interferon regulatory factor

Jak:

Janus kinase

LAM:

Lipoarabinomannan

LPS:

Lipopolysaccharide

LTBI:

Latent TB infection

MDR:

Multi-drug resistant

MHC:

Major histocompatibility complex

MR:

Mannose receptor

Mtb:

Mycobacterium tuberculosis

MGC:

Multinucleated giant cell

NADPH:

Nicotinamide adenine dinucleotide phosphate (reduced)

NF-κB:

Nuclear factor (NF)-κB

NRAMP:

Natural resistance-associated macrophage protein

NO:

Nitric oxide

N0S2:

Inducible nitric oxide synthase

PAMP:

Pathogen-associated molecular pattern

PBMC:

Peripheral blood mononuclear cell

PG:

Phagosome

PI3P:

Phosphatidyl inositol 3-phosphate

PL:

Phagolysosome

PRR:

Pattern-recognition receptor

RNI:

Reactive nitrogen intermediates

ROI:

Reactive oxygen intermediates

SNO:

S-nitrosothiol

SP:

Surfactant protein

STAT:

Signal transducer and activator of transcription

TLR:

Toll-like receptor

TNF:

Tumour necrosis factor alpha

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MacMicking, J.D., McKinney, J.D. (2003). Macrophage Immunity and Mycobacterium tuberculosis . In: Gordon, S. (eds) The Macrophage as Therapeutic Target. Handbook of Experimental Pharmacology, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55742-2_22

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  • Print ISBN: 978-3-642-62919-8

  • Online ISBN: 978-3-642-55742-2

  • eBook Packages: Springer Book Archive

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