Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression

Galmbacher, Katharina; Heisig, Martin; Hotz, Christian; Wischhusen, Joerg; Galmiche, Antoine; Bergmann, Birgit; Gentschev, Ivaylo; Goebel, Werner; Rapp, Ulf R.; Fensterle, Joachim

doi:10.1371/journal.pone.0009572

Cited by 53 publications

(30 citation statements)

References 37 publications

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“…TAMs possess characteristics of the M2 state [22] and the wound healing/regulatory states [29]. In animal models, TAMs promote tumor growth and metastases [38,39]. While we hypothesize that these PCNA ?…”

Section: Discussionmentioning

confidence: 90%

Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity

Mukhtar

Moore

Nseyo

et al. 2011

Breast Cancer Res Treat

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African American and Hispanic women develop more triple negative breast cancer at younger ages than Caucasian women. The frequently observed association between race and socioeconomic status (SES) has confounded our understanding of the outcomes disparities seen in these groups. Given the association between inflammatory cells and high-grade, triple negative tumors, we sought to investigate whether differences in the presence of these cells varies by race. We evaluated breast tumor specimens for the presence PCNA+ tumor-associated macrophages (TAMs) in consecutive cases from a county hospital serving primarily un- or under-insured patients. All patients in this cohort had elevated PCNA + TAM levels. Higher PCNA + TAM counts were associated with hormone receptor (HR) negative tumors and non-Caucasian ethnicity. Hispanic women specifically had significantly higher PCNA + TAM counts than Caucasian patients and shorter disease-free survival. These findings implicate immune function in the development of aggressive breast cancer and suggest a possible link between SES and the inflammatory response.

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Section: Discussionmentioning

confidence: 90%

Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity

Mukhtar

Moore

Nseyo

et al. 2011

Breast Cancer Res Treat

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“…DNA vaccination against legumain, a member of the asparaginyl endopeptidase family overexpressed by TAM, results in immune elimination of TAM and strongly reduced breast tumor growth and metastasis (Luo et al, 2006). Similarly, depletion of TAM in transgenic MMTV-HER-2 mice by an attenuated strain of Shigella flexneri, which induces apoptosis specifically in macrophages, resulted in a block of tumor growth and even tumor regression (Galmbacher et al, 2010).…”

Section: Clinical Relevance Of Tumor-associated Macrophages In Breastmentioning

confidence: 99%

Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions

Laoui¹,

Movahedi²,

Overmeire³

et al. 2011

Int. J. Dev. Biol.

267

197

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“…⌬aroA strains of S. Typhimurium and S. flexneri are defective in intracellular survival due to their inability to synthesize aromatic amino acids (8,16,20,21). An intracellular survival assay and confocal microscopic analysis were performed with ⌬aroA strains of S. Typhimurium and S. flexneri.…”

Section: Curcumin Modulates Fate Of Intracellular Bacteriamentioning

confidence: 99%

Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin

Marathe

Sen

Dasgupta

et al. 2012

Antimicrob Agents Chemother

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Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter-and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria. C urcumin, a pigment from turmeric, is known to have a vast array of therapeutic potential, ranging from anti-inflammatory to anticancer effects. It has also been shown to exhibit antimicrobial effects. However, its role as an antimicrobial agent remains controversial. Curcumin shows its antimicrobial effect against Helicobacter pylori (14,19), Bacillus subtilis (38), Plasmodium falciparum (11, 34), etc. On the other hand, the role of curcumin as a promicrobial has been demonstrated in Leishmania (1) and Salmonella spp. (30). Curcumin is known to suppress the type 1 immune response (1, 24), which is important for the clearance of intracellular pathogens. In the following study, we sought to assess the effect of curcumin on the virulence of a few medically important intracellular foodborne pathogens.The constant battle between the pathogen and host highlights the crux of host-pathogen interactions. The host has a repertoire of combative cells to keep the infection at bay (15,28,40). Similarly, pathogens employ different strategies to hijack the host immune system (15,28,40). Once the pathogen is sensed by the host immune system, it initiates an inflammatory response, recruiting different phagocytic cells to the site of infection. Macrophages, the key players in eliminating pathogens (32,46), phagocytose the bacteria and use various tools to clear pathogens (27,32,43). The foremost tool is lysosomal degradation of the invading pathogen. During the process of phagocytosis, the bacteria or any foreig...

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Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression

Cited by 53 publications

References 37 publications

Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity

Elevated PCNA+ tumor-associated macrophages in breast cancer are associated with early recurrence and non-Caucasian ethnicity

Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions

Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin

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