Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells

Amy S. McKee, Matthew A. Burchill, Michael Munks, Lei Jin, John W. Kappler, Rachel S. Friedman, Jordan Jacobelli, Philippa Marrack

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigenbearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number12
DOIs
StatePublished - Mar 19 2013
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class II
Antigen Presentation
Aluminum
Cell Communication
Dendritic Cells
Deoxyribonucleases
Salts
T-Lymphocytes
DNA
Antigens
Vaccines
Lymph Nodes
Muscles
CD4 Antigens
Peritoneal Cavity
Cell Movement
Immunization
Cytoplasm
Injections
Genes

Keywords

  • Interaction time
  • Lymph node
  • Multiphoton imaging

ASJC Scopus subject areas

  • General

Cite this

Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells. / McKee, Amy S.; Burchill, Matthew A.; Munks, Michael; Jin, Lei; Kappler, John W.; Friedman, Rachel S.; Jacobelli, Jordan; Marrack, Philippa.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 12, 19.03.2013.

Research output: Contribution to journalArticle

@article{e968e43b19cf4a1c81a5e62851718b81,
title = "Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells",
abstract = "Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigenbearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.",
keywords = "Interaction time, Lymph node, Multiphoton imaging",
author = "McKee, {Amy S.} and Burchill, {Matthew A.} and Michael Munks and Lei Jin and Kappler, {John W.} and Friedman, {Rachel S.} and Jordan Jacobelli and Philippa Marrack",
year = "2013",
month = "3",
day = "19",
doi = "10.1073/pnas.1300392110",
language = "English (US)",
volume = "110",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "12",

}

TY - JOUR

T1 - Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells

AU - McKee, Amy S.

AU - Burchill, Matthew A.

AU - Munks, Michael

AU - Jin, Lei

AU - Kappler, John W.

AU - Friedman, Rachel S.

AU - Jacobelli, Jordan

AU - Marrack, Philippa

PY - 2013/3/19

Y1 - 2013/3/19

N2 - Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigenbearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.

AB - Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigenbearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.

KW - Interaction time

KW - Lymph node

KW - Multiphoton imaging

UR - http://www.scopus.com/inward/record.url?scp=84875278101&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875278101&partnerID=8YFLogxK

U2 - 10.1073/pnas.1300392110

DO - 10.1073/pnas.1300392110

M3 - Article

VL - 110

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 12

ER -