IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection

Dong Liu; Xiangyun Yin; Sam J. Olyha; Manuela Sales L. Nascimento; Pei Chen; Theresa White; Uthaman Gowthaman; Tingting Zhang; Jake A. Gertie; Biyan Zhang; Lan Xu; Marina Yurieva; Lesley Devine; Adam Williams; Stephanie C. Eisenbarth

doi:10.1016/j.immuni.2019.05.011

IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α⁺ Dendritic Cells Promotes Listeria monocytogenes Infection

Dong Liu, Xiangyun Yin, Sam J. Olyha, Manuela Sales L. Nascimento, Pei Chen, Theresa White, Uthaman Gowthaman, Tingting Zhang, Jake A. Gertie, Biyan Zhang, Lan Xu, Marina Yurieva, Lesley Devine, Adam Williams^*, Stephanie C. Eisenbarth

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Type 1 CD8α⁺ conventional dendritic cells (cDC1s) are required for CD8⁺ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8⁺ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8⁺ T cell activation.

Original language	English (US)
Pages (from-to)	64-76.e7
Journal	Immunity
Volume	51
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2019.05.011
State	Published - Jul 16 2019

Funding

We would like to thank M. Firla for technical assistance, M. Wimsatt for the illustration, L.A. Zenewicz and H. Agaisse for providing strains of Lm, E. Hoffman for technical guidance regarding phagosome analysis, T. Zhang for help with imaging, S. Calabro and J. Krishnaswamy for helpful discussions, and E.G. Pamer for RFP-Lm and critical review of the manuscript. This work was supported by a CIHR postdoctoral fellowship (to D.L.), P01 HL132819 (to S.C.E.), R01 AI108829 (to S.C.E.), and R21 AI135221 and R21 AI133440 (to A.W.).

Keywords

DOCK8
IL-10
Listeria monocytogenes
T cell
dendritic cells
iNOS
macrophage
marginal zone B cells
spleen

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2019.05.011

Cite this

Liu, D., Yin, X., Olyha, S. J., Nascimento, M. S. L., Chen, P., White, T., Gowthaman, U., Zhang, T., Gertie, J. A., Zhang, B., Xu, L., Yurieva, M., Devine, L., Williams, A., & Eisenbarth, S. C. (2019). IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α⁺ Dendritic Cells Promotes Listeria monocytogenes Infection. Immunity, 51(1), 64-76.e7. https://doi.org/10.1016/j.immuni.2019.05.011

@article{2c035199e71747bc9f5977b10649305f,

title = "IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection",

abstract = "Type 1 CD8α+ conventional dendritic cells (cDC1s) are required for CD8+ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8+ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8+ T cell activation.",

keywords = "DOCK8, IL-10, Listeria monocytogenes, T cell, dendritic cells, iNOS, macrophage, marginal zone B cells, spleen",

author = "Dong Liu and Xiangyun Yin and Olyha, {Sam J.} and Nascimento, {Manuela Sales L.} and Pei Chen and Theresa White and Uthaman Gowthaman and Tingting Zhang and Gertie, {Jake A.} and Biyan Zhang and Lan Xu and Marina Yurieva and Lesley Devine and Adam Williams and Eisenbarth, {Stephanie C.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = jul,

day = "16",

doi = "10.1016/j.immuni.2019.05.011",

language = "English (US)",

volume = "51",

pages = "64--76.e7",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "1",

}

Liu, D, Yin, X, Olyha, SJ, Nascimento, MSL, Chen, P, White, T, Gowthaman, U, Zhang, T, Gertie, JA, Zhang, B, Xu, L, Yurieva, M, Devine, L, Williams, A & Eisenbarth, SC 2019, 'IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α⁺ Dendritic Cells Promotes Listeria monocytogenes Infection', Immunity, vol. 51, no. 1, pp. 64-76.e7. https://doi.org/10.1016/j.immuni.2019.05.011

TY - JOUR

T1 - IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection

AU - Liu, Dong

AU - Yin, Xiangyun

AU - Olyha, Sam J.

AU - Nascimento, Manuela Sales L.

AU - Chen, Pei

AU - White, Theresa

AU - Gowthaman, Uthaman

AU - Zhang, Tingting

AU - Gertie, Jake A.

AU - Zhang, Biyan

AU - Xu, Lan

AU - Yurieva, Marina

AU - Devine, Lesley

AU - Williams, Adam

AU - Eisenbarth, Stephanie C.

PY - 2019/7/16

Y1 - 2019/7/16

N2 - Type 1 CD8α+ conventional dendritic cells (cDC1s) are required for CD8+ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8+ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8+ T cell activation.

AB - Type 1 CD8α+ conventional dendritic cells (cDC1s) are required for CD8+ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8+ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8+ T cell activation.

KW - DOCK8

KW - IL-10

KW - Listeria monocytogenes

KW - T cell

KW - dendritic cells

KW - iNOS

KW - macrophage

KW - marginal zone B cells

KW - spleen

UR - http://www.scopus.com/inward/record.url?scp=85067975962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067975962&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2019.05.011

DO - 10.1016/j.immuni.2019.05.011

M3 - Article

C2 - 31231033

AN - SCOPUS:85067975962

SN - 1074-7613

VL - 51

SP - 64-76.e7

JO - Immunity

JF - Immunity

IS - 1

ER -