Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Aug;96(2):233-44.
doi: 10.1189/jlb.4RI0214-090R. Epub 2014 Jun 4.

Intracellular immunity: finding the enemy within--how cells recognize and respond to intracellular pathogens

Jerry C H Tam  1 , David A Jacques  2
Affiliations

Intracellular immunity: finding the enemy within--how cells recognize and respond to intracellular pathogens

Jerry C H Tam et al. J Leukoc Biol. 2014 Aug.

Abstract

Historically, once a cell became infected, it was considered to be beyond all help. By this stage, the invading pathogen had breached the innate defenses and was beyond the reach of the humoral arm of the adaptive immune response. The pathogen could still be removed by cell-mediated immunity (e.g., by NK cells or cytotoxic T lymphocytes), but these mechanisms necessitated the destruction of the infected cell. However, in recent years, it has become increasingly clear that many cells possess sensor and effector mechanisms for dealing with intracellular pathogens. Most of these mechanisms are not restricted to professional immune cells nor do they all necessitate the destruction of the host. In this review, we examine the strategies that cells use to detect and destroy pathogens once the cell membrane has been penetrated.

Keywords: DAMP; PAMP; pathogen sensing.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Localization and classification of intracellular sensors.
Intracellular pathogen sensors can be classified according to their mechanism of recognition, be it via PAMPs and DAMPs, RNA, DNA, or other features of a pathogen-replication cycle. Most of these sensors are soluble, cytoplasmic proteins. TLR, NLR, and galectin-8 sensing of burst endosomes detect danger associated with infection. RNA is detected by RLRs, PKR, OAS, DDX1 and -21, and DHX36. DNA is sensed by transcription by RNA Pol III to RNA products, ALRs, DAI, cGAS, DNA PK, MRE11, DDX41 and -60, and DHX9 and -36. Other proteins—LSm14A, LRRFIP1, and the HMGB family—have been found to be important in the detection of both types of nucleic acids. Other detection methods for pathogens, based on their replication cycle, are present. Mx GTPases and TRIM5α sense the virus capsid coat, with TRIM21 detecting antibody carried into the cytosol on incoming pathogens. Tetherin is able to sense budding events from the plasma membrane. NALP3, NLR family, PYD-containing 3.
Figure 2.
Figure 2.. Domain architecture of intracellular sensors.
PRRs of the TLR, NLR, RLR, ALR, and TRIM families possess similar binding and signaling domains, suggesting that activation leads to similar innate programs of responses against pathogens. Note that the death fold is conserved in CARD, DD, and PYDs, with PYDs related to the PRYSPRY domains. NACHT, Nucleotide-binding and CARD.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rajewsky K. (1996) Clonal selection and learning in the antibody system. Nature 381, 751–758 - PubMed
    1. Fontana M. F., Vance R. E. (2011) Two signal models in innate immunity. Immunol. Rev. 243, 26–39 - PubMed
    1. Janeway C. A., Jr., (2013) Pillars article: approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 1989. 54: 1–13. J. Immunol. 191, 4475–487 - PubMed
    1. Medzhitov R. (2009) Approaching the asymptote: 20 years later. Immunity 30, 766–775 - PubMed
    1. Medzhitov R. (2013) Pattern recognition theory and the launch of modern innate immunity. J. Immunol. 191, 4473–4474 - PubMed

Publication types