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Dendritic cell response to HIV-1 is controlled by differentiation programs in the cells and strain-specific properties of the virus

Nasi, Aikaterini; Amu, Sylvie; Göthlin, Mårten; Jansson, Marianne LU ; Nagy, Noemi; Chiodi, Francesca and Réthi, Bence (2017) In Frontiers in Immunology 8(MAR).
Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or,... (More)

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cytokines, Dendritic cell, HIV-1, IL-12, Infection
in
Frontiers in Immunology
volume
8
issue
MAR
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85017242046
  • wos:000395864400001
DOI
10.3389/fimmu.2017.00244
language
English
LU publication?
yes
id
2d47315d-6680-435a-943e-3cac20a30466
date added to LUP
2017-05-23 11:20:44
date last changed
2018-11-21 21:32:14
@article{2d47315d-6680-435a-943e-3cac20a30466,
  abstract     = {<p>Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.</p>},
  articleno    = {244},
  author       = {Nasi, Aikaterini and Amu, Sylvie and Göthlin, Mårten and Jansson, Marianne and Nagy, Noemi and Chiodi, Francesca and Réthi, Bence},
  keyword      = {Cytokines,Dendritic cell,HIV-1,IL-12,Infection},
  language     = {eng},
  month        = {03},
  number       = {MAR},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Dendritic cell response to HIV-1 is controlled by differentiation programs in the cells and strain-specific properties of the virus},
  url          = {http://dx.doi.org/10.3389/fimmu.2017.00244},
  volume       = {8},
  year         = {2017},
}