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Table 2 The use of iMphs to study macrophage-pathogen interactions

From: Macrophages derived from pluripotent stem cells: prospective applications and research gaps

Infectious agent

Reference

Main findings

Salmonella typhi,

S. typhimurium

Hale et al. [45]

iMphs are phagocytic and up-regulate inflammation-related genes in response to the infection

P. aeruginosa

Ackermann et al. [46]

Co-administration of P. aeruginosa and human iMphs to immunodeficient mice prevents the development of the infection; iMph administration shortly after the infection with P. aeruginosa (4 h) decreases infection severity

S. aureus

Hashtchin et al. [98]

Intratracheal injection of iMphs to immunodeficient humanized mice challenged with S aureus (incuding methicillin-resistant strain) reduces S aureus load, decreases granulocytic infiltration and diminishes lung pathology. Transcriptomic analysis: compared to MDMs, iMphs respond to the infection by a more profound upregulation of inflammatory genes early after infection, however the expression normalizes faster than in MDMs

L. major

O’Kneefe et al. [91]

After the infection, iMphs contain a higher level of intracellular L. major compared to THP-1, mouse and human bone marrow-derived macrophages

M. tuberculosis

Nenasheva et al. [33]

iMphs phagocyte and restrict Mtb growth in vitro

Bernard et al. [90]

iMph infection with either virulent Mtb or the attenuated ESX-1-deficient Mtb mutant allowed to identify a role of ESX-1 secretion system of Mtb in the formation of autophagosomes and the subsequent Mtb escape from autophagosomes to the cytosol

Haake et al. [47]

iMphs derived from patients with a complete or partial deficiency in IFN-γR2, IFN-γR1 or STAT1 demonstrate a defective upregulation of HLA-DR, CD64, CD38 and CD282 in response to IFNγ, a decreased phosphorylation of STAT1, no-to-little clearance of BCG. Additionally, STAT1-deficient iMphs have a disturbed production of ROS

Han et al. [89]

iMphs are suitable to search for new anti-infectious drugs: the screening of a library of 3.716 compounds for their anti-Mtb activity was performed and a novel anti-Mtb compound, 10-DEBC, was identified

HIV-1

van Wilgenburg et al. [27]

iMphs are infectable with HIV-1

Vaughan-Jackson et al. [92]

iMphs are infectable with HIV-1 and ZIKV

Taylor et al. [96]

CRISPR/Cas9 engineered iMphs with depleted USP18 exhibit: an increased reactivity to IFNI, a prolonged STAT1 and STAT2 phosphorylation; an enhanced expression of IFN‐stimulated genes; an increased restriction of HIV replication

ZIKV, DENV

Lang et al. [93]

Differences in iMph response to DENV and ZIKV have been demonstrated: DENV induced a higher inflammatory response, a higher production of MIF and a decreased iMph migration; ZIKV inhibited NF-kB signaling pathway

  1. DENV dengue virus, MIF macrophage migration inhibitory factor, ZIKV zika virus