Macrophage activation in human diseases

Schultze, Joachim L.; Schmieder, Astrid; Goerdt, Sergij

doi:10.1016/j.smim.2015.07.003

Cited by 109 publications

(83 citation statements)

References 101 publications

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“…Macrophages form an important line of host defense in innate immune system against infections (Aderem, 2003; Tam and Aderem, 2014; Zhang and Wang, 2014; Divangahi et al, 2015; Hume, 2015; Schultze et al, 2015). Some studies employ macrophage cell lines to understand the interaction of pathogens with immune cells that may not mimic the true characteristics of primary cells.…”

Section: Discussionmentioning

confidence: 99%

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Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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Otitis media (OM) is a broad term describing a group of infectious and inflammatory disorders of the middle ear. Despite antibiotic therapy, acute OM can progress to chronic suppurative otitis media (CSOM) characterized by ear drum perforation and purulent discharge. Pseudomonas aeruginosa is the most common pathogen associated with CSOM. Although, macrophages play an important role in innate immune responses but their role in the pathogenesis of P. aeruginosa-induced CSOM is not known. The objective of this study is to examine the interaction of P. aeruginosa with primary macrophages. We observed that P. aeruginosa enters and multiplies inside human and mouse primary macrophages. This bacterial entry in macrophages requires both microtubule and actin dependent processes. Transmission electron microscopy demonstrated that P. aeruginosa was present in membrane bound vesicles inside macrophages. Interestingly, deletion of oprF expression in P. aeruginosa abrogates its ability to survive inside macrophages. Our results suggest that otopathogenic P. aeruginosa entry and survival inside macrophages is OprF-dependent. The survival of bacteria inside macrophages will lead to evasion of killing and this lack of pathogen clearance by phagocytes contributes to the persistence of infection in CSOM. Understanding host–pathogen interaction will provide novel avenues to design effective treatment modalities against OM.

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Section: Discussionmentioning

confidence: 99%

“…One of the principal components of the innate immune system are macrophages (Tam and Aderem, 2014; Divangahi et al, 2015; Hume, 2015; Schultze et al, 2015). They are considered as “professional phagocytes” that play a crucial role in eradication of pathogens through phagocytosis leading to clearance of infection (Aderem, 2003).…”

Section: Introductionmentioning

confidence: 99%

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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“…M2 macrophages are specified as expression of arginase, and surface markers CD163, CD206 and CD301 that are not expressed by M1 macrophages [11,23,24,26,[34][35][36][37][38][39][40]. Macrophage polarization has been shown to regulate a variety of biological processes, as recently nicely reviewed [41][42][43]. TIPE2 was recently found to inhibit inducible nitric oxide synthase (iNOS) and thus generation of nitric oxide, resulting in suppression of inflammation [11,[21][22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization

Xian

Yang

et al. 2016

Cell Physiol Biochem

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Background/Aims: We have recently shown that macrophage polarization may alter the pathogenesis and severity of systemic lupus erythematosus (SLE). However, a practical approach to modulate macrophage polarization in vivo is so far not available. In the current study, we aimed to use tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) to regulate macrophage polarization in vitro and in vivo, and to study the effects on experimental SLE. Methods: We prepared adeno-associated virus carrying TIPE2 (AAV-TIPE2). We induced experimental SLE in mice with an activated lymphocyte-derived DNA (ALD-DNA) method. We examined the effects of TIPE2 overexpression on macrophage polarization in vitro, and in vivo in the SLE model. We also examined the effects of TIPE2 overexpression on the severity of SLE, by serum anti-dsDNA autoantibody, renal pathological changes, and urine protein levels. Results: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, renal pathological changes, and increases in urine protein levels. TIPE2 overexpression by AAV-TIPE2 induced macrophage polarization to a M2 phenotype, in vitro and in vivo in the SLE mouse model. TIPE2 overexpression significantly decreased SLE severity. Conclusion: TIPE2 alleviates experimental SLE through induction of macrophage polarization to a M2 phenotype, which may be used as a promising therapeutic strategy for treating SLE.

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“…Because of their important and diverse functions in regulating immune responses and metabolism, dysregulated macrophage polarization is frequently associated with disease (Schultze et al, 2015). Here we expand our understanding of macrophage phenotype switching 325 by showing on the molecular level that engagement of MSR1 in IL-4-activated macrophages results in the activation of the JNK signalling pathway, thereby inducing a shift from an anti-inflammatory to a proinflammatory phenotype.…”

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confidence: 82%

Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages

Guo

Härtlová

Prescott

et al. 2018

Preprint

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SummaryAlternatively activated M2 macrophages play an important role in maintenance of tissue homeostasis by scavenging dead cells, cell debris and lipoprotein aggregates via phagocytosis. Using proteomics, we investigated how alternative activation, driven by IL-4, modulated the phagosomal proteome to control macrophage function. Our data indicate that alternative activation enhances homeostatic functions such as proteolysis, lipolysis and nutrient transport. Intriguingly, we identified the enhanced recruitment of the TAK1/MKK7/JNK signalling complex to phagosomes of IL-4 activated macrophages. The recruitment of this signalling complex was mediated through K63-polyubiquitylation of the macrophage scavenger receptor 1 (MSR1). Triggering of MSR1 in IL-4 activated macrophages leads to enhanced JNK activation, thereby promoting a phenotypic switch from an anti-inflammatory to a pro-inflammatory state, which was abolished upon MSR1 deletion or JNK inhibition. Moreover, MSR1 K63-polyubiquitylation correlated with the activation of JNK signalling in ovarian cancer tissue from human patients, suggesting that it may be relevant for macrophage phenotypic shift in vivo. Altogether, we identified that MSR1 signals through JNK via K63-polyubiquitylation and provide evidence for the receptor’s involvement in macrophage polarization.

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Macrophage activation in human diseases

Cited by 109 publications

References 101 publications

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization

Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages

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