PMID- 30357820
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20231213
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 156
IP  - 2
DP  - 2019 Feb
TI  - Plasticity of antimicrobial and phagocytic programs in human macrophages.
PG  - 164-173
LID - 10.1111/imm.13013 [doi]
AB  - Macrophage (MPhi) polarization is triggered during the innate immune response to 
      defend against microbial pathogens, but can also contribute to disease 
      pathogenesis. In a previous study, we found that interleukin-15 (IL-15) -derived 
      classically activated macrophages (M1 MPhi) have enhanced antimicrobial activity, 
      whereas IL-10-derived alternatively activated macrophages (M2 MPhi) were highly 
      phagocytic but lacked antimicrobial activity. Given that the ability to modulate 
      MPhi polarization from M2 MPhi to M1 MPhi may promote a more effective immune response 
      to infection, we investigated the plasticity of these MPhi programs. Addition of 
      IL-10 to M1 MPhi induced M2-like MPhi, but IL-15 had little effect on M2 MPhi. We 
      determined the set of immune receptors that are present on M2 MPhi, elucidating two 
      candidates for inducing plasticity of M2 MPhi, Toll-like receptor 1 (TLR1) and 
      interferongamma (IFN-gamma) receptor 1. Stimulation of M2 MPhi with TLR2/1 ligand (TLR2/1L) 
      or IFN-gamma alone was not sufficient to alter M2 MPhi phenotype or function. However, 
      co-addition of TLR2/1L and IFN-gamma re-educated M2 MPhi towards the M1 MPhi phenotype, 
      with a decrease in the phagocytosis of lipids and mycobacteria, as well as 
      recovery of the vitamin-D-dependent antimicrobial pathway compared with M2 MPhi 
      maintained in polarizing conditions. Similarly, treatment of M2 MPhi with both 
      TLR2/1L and anti-IL-10 neutralizing antibodies led to polarization to the M1-like 
      MPhi phenotype and function. Together, our data demonstrate an approach to induce 
      MPhi plasticity that provides the potential for re-educating MPhi function in human 
      mycobacterial disease to promote host defense and limit pathogenesis.
CI  - (c) 2018 John Wiley & Sons Ltd.
FAU - Montoya, Dennis
AU  - Montoya D
AD  - Department of Molecular, Cell, and Developmental Biology, University of 
      California, Los Angeles, CA, USA.
FAU - Mehta, Manali
AU  - Mehta M
AD  - Division of Dermatology, Department of Medicine, David Geffen School of Medicine, 
      University of California, Los Angeles, CA, USA.
FAU - Ferguson, Benjamin G
AU  - Ferguson BG
AD  - Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ, 
      USA.
FAU - Teles, Rosane M B
AU  - Teles RMB
AD  - Division of Dermatology, Department of Medicine, David Geffen School of Medicine, 
      University of California, Los Angeles, CA, USA.
FAU - Krutzik, Stephan R
AU  - Krutzik SR
AD  - Division of Dermatology, Department of Medicine, David Geffen School of Medicine, 
      University of California, Los Angeles, CA, USA.
FAU - Cruz, Daniel
AU  - Cruz D
AD  - Division of Cardiology, Department of Medicine, David Geffen School of Medicine, 
      University of California, Los Angeles, CA, USA.
FAU - Pellegrini, Matteo
AU  - Pellegrini M
AD  - Department of Molecular, Cell, and Developmental Biology, University of 
      California, Los Angeles, CA, USA.
FAU - Modlin, Robert L
AU  - Modlin RL
AUID- ORCID: 0000-0003-4720-031X
AD  - Division of Dermatology, Department of Medicine, David Geffen School of Medicine, 
      University of California, Los Angeles, CA, USA.
LA  - eng
GR  - R01 AI022553/AI/NIAID NIH HHS/United States
GR  - R01 AR040312/AR/NIAMS NIH HHS/United States
GR  - NIH3P50AR06302/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20181111
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Interferon)
RN  - 0 (TLR1 protein, human)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 1)
RN  - 0 (Toll-Like Receptor 2)
MH  - Cytokines/immunology
MH  - Female
MH  - Humans
MH  - *Macrophage Activation
MH  - Macrophages/*immunology/pathology
MH  - Male
MH  - Mycobacterium Infections/*immunology/pathology
MH  - *Phagocytosis
MH  - Receptors, Interferon/immunology
MH  - Toll-Like Receptor 1/*immunology
MH  - Toll-Like Receptor 2/*immunology
MH  - Interferon gamma Receptor
PMC - PMC6328994
OTO - NOTNLM
OT  - antimicrobial
OT  - macrophage
OT  - mycobacteria
OT  - phagocytosis
OT  - polarization
EDAT- 2018/10/26 06:00
MHDA- 2019/08/06 06:00
PMCR- 2020/02/01
CRDT- 2018/10/26 06:00
PHST- 2018/08/15 00:00 [received]
PHST- 2018/10/01 00:00 [accepted]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2020/02/01 00:00 [pmc-release]
AID - IMM13013 [pii]
AID - 10.1111/imm.13013 [doi]
PST - ppublish
SO  - Immunology. 2019 Feb;156(2):164-173. doi: 10.1111/imm.13013. Epub 2018 Nov 11.