Comparison of human monocyte derived macrophages and THP1-like macrophages as in vitro models for M. tuberculosis infection

Madhvi, Abhilasha; Mishra, Hridesh; Leisching, Gina; Mahlobo, PZ; Baker, Bienyameen

doi:10.1016/j.cimid.2019.101355

Cited by 40 publications

(53 citation statements)

References 25 publications

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“…The THP-1 cell line has been described to be a suitable model to study macrophage differentiation, functions and responses to external stimuli from the micro and macro-environment [45,53,54].…”

Section: Discussionmentioning

confidence: 99%

Modulating Tumor-Associated Macrophage Polarization by Synthetic and Natural PPARγ Ligands as a Potential Target in Breast Cancer

Gionfriddo

Plastina

Augimeri

et al. 2020

Cells

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Activation of peroxisome proliferator-activated receptor gamma (PPARγ) elicits anti-proliferative effects on different tumor cells, including those derived from breast cancer. PPARγ is also expressed in several cells of the breast tumor microenvironment, among which tumor associated macrophages (TAMs) play a pivotal role in tumor progression and metastasis. We explored the ability of synthetic and natural PPARγ ligands to modulate TAM polarization. The ligands included rosiglitazone (BRL-49653), and two docosahexaenoic acid (DHA) conjugates, N-docosahexaenoyl ethanolamine (DHEA) and N-docosahexaenoyl serotonin (DHA-5-HT). Human THP-1 monocytic cells were differentiated into M0, M1 and M2 macrophages that were characterized by qRT-PCR, ELISA and western blotting. A TAM-like phenotypic state was generated by adding two different breast cancer cell conditioned media (BCC-CM) to the cultures. Macrophages exposed to BCC-CM concomitantly exhibited M1 and M2 phenotypes. Interestingly, rosiglitazone, DHEA and DHA-5-HT attenuated cytokine secretion by TAMs, and this effect was reversed by the PPARγ antagonist GW9662. Given the key role played by PPARγ in the crosstalk between cancer cells and TAMs in tumor progression, its activation via endogenous or synthetic ligands may lead to novel strategies that target both epithelial neoplastic cells and the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Modulating Tumor-Associated Macrophage Polarization by Synthetic and Natural PPARγ Ligands as a Potential Target in Breast Cancer

Gionfriddo

Plastina

Augimeri

et al. 2020

Cells

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“…Firstly we sought to determine whether OASL upregulation was dependent on pathogenicity and virulence of mycobacteria by using the non-pathogenic M. bovis BCG strain, as well as the closely related hypo- and hypervirulent M. tuberculosis strains (Fig.1). Using THP-1 macrophages for our infection model [25], our results indicate that OASL is upregulated 24 h p.i in response to pathogenic M.tb infection only. Although M. bovis BCG does not induce its expression, it is likely that this occurs at a later time-point.…”

Section: Discussionmentioning

confidence: 99%

2′-5′-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion

Leisching

Ali

Cole

et al. 2019

Preprint

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Host cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1β, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.

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“…This notwithstanding, whereas U937 macrophages appeared to differ substantially from hMDMs, THP-1 cells are assumed to be representative of the macrophages. THP-1 and hMDMs showed similar bacterial phagocytosis and host response to infection with M. tuberculosis , as well as similar cytokine/chemokine type and secretion [ 35 ]. Despite the lack of comparative studies that specifically investigate NTM-host response in different cellular substrates, the majority of researches have employed THP-1 cells for DST on NTM.…”

Section: Static Intracellular Infection Modelsmentioning

confidence: 99%

“…Most commonly, shorter assays, consisting of 24–48 h of drug exposure, are preferred to ensure the survival of macrophages until the end of the test. However, cytotoxicity assays revealed consistent viability up to day 16 post-infection of THP-1 cells with mycobacterial cells [ 35 ]. In the event of an extended length of the assay, the estimation of cell viability and analysis of drug stability are recommended.…”

Section: Static Intracellular Infection Modelsmentioning

confidence: 99%

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

et al. 2020

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Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds.

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Comparison of human monocyte derived macrophages and THP1-like macrophages as in vitro models for M. tuberculosis infection

Cited by 40 publications

References 25 publications

Modulating Tumor-Associated Macrophage Polarization by Synthetic and Natural PPARγ Ligands as a Potential Target in Breast Cancer

Modulating Tumor-Associated Macrophage Polarization by Synthetic and Natural PPARγ Ligands as a Potential Target in Breast Cancer

2′-5′-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

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