Differential immune response of adipocytes to virulent and attenuated Mycobacterium tuberculosis

Kim, Jong Seok; Ryu, Min Jeong; Byun, Eui Hong; Kim, Woo Sik; Whang, Jake; Min, Ki Nam; Shong, Minho; Kim, Hwa Jung; Shin, Sung Jae

doi:10.1016/j.micinf.2011.07.002

Cited by 20 publications

(26 citation statements)

References 46 publications

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“…Usually, it is expected a decrease of cytokine secretion by host cells that were incubated with pathogens fixed with formaldehyde [31,32]. Therefore, we were surprised when concentrations of IL-6 and IL-8 were significantly higher in culture supernatants of A549 cells incubated with formaldehyde-fixed P. brasiliensis compared to supernatants from A549 cultures incubated with live yeasts.…”

Section: Discussionmentioning

confidence: 96%

Paracoccidioides brasiliensis induces secretion of IL-6 and IL-8 by lung epithelial cells. Modulation of host cytokine levels by fungal proteases

Maza¹,

Oliveira²,

Toledo

et al. 2012

Microbes and Infection

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Paracoccidioides brasiliensis is a pathogenic, dimorphic fungus that causes paracoccidioidomycosis, a systemic human mycosis that is highly prevalent in Latin America. In this study, we demonstrated that P. brasiliensis yeasts induced interleukin (IL)-8 and IL-6 secretion by human lung epithelial A549 cells. However, tumor necrosis factor-α and interferon-γ were undetectable in these cultures. Moreover, P. brasiliensis yeasts induced activation of p38 mitogen-activated protein kinase (MAPK), c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2 in A549 cells, and IL-8 and IL-6 secretion promoted by this fungus was dependent on activation of p38 MAPK and ERK 1/2. In addition, IL-8 and IL-6 levels were significantly higher in culture supernatants of A549 cells that were incubated with formaldehyde-fixed P. brasiliensis compared to cultures of cells that were infected with live yeasts. Our results indicate that the observed cytokine level differences were due to protease expression, in live yeasts, that degraded these cytokines. Degradation of human recombinant IL-8 and IL-6 by live P. brasiliensis was inhibited by AEBSF and aprotinin, suggesting that these proteases belong to a family of serine proteases. This is the first report showing that P. brasiliensis may modulate host inflammation by expressing proteases that degrade proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 96%

Paracoccidioides brasiliensis induces secretion of IL-6 and IL-8 by lung epithelial cells. Modulation of host cytokine levels by fungal proteases

Maza¹,

Oliveira²,

Toledo

et al. 2012

Microbes and Infection

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“…We observed differences in cytokine mRNA levels between the two physiologic forms, even if not paralleled by differential cytokine secretion. Recently, it has been shown that highly virulent strains of Mtb suppress cytokine gene expression compared to less virulent strains [21,22], suggesting that dormant Mtb may be detected by the macrophage as a less virulent form.…”

Section: Discussionmentioning

confidence: 99%

Infection of human THP-1 cells with dormant Mycobacterium tuberculosis

Iona

Pardini

Gagliardi

et al. 2012

Microbes and Infection

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“…To explore M. canettii interactions with 3T3-L1 pre-adipocytes and mature adipocytes compare to M. tuberculosis (Neyrolles et al, 2006; Kim et al, 2011), the quantification of the ratio of infected cells/total cells and the number of intracellular bacilli/cell were performed on a random selection of 10 microscope fields after Ziehl-Neelsen staining of infected cells at day 3 p.i. (see Supplementary Data S1).…”

Section: Resultsmentioning

confidence: 99%

“…Adipose tissues have been previously supposed to act as long-term sanctuaries sheltering Mycobacterium tuberculosis , the major agent of human tuberculosis worldwide (Neyrolles et al, 2006; Kim et al, 2011; Agarwal et al, 2014, 2016; Rastogi et al, 2016). In vitro experiments were conducted using murine 3T3-L1 mature adipocytes (Neyrolles et al, 2006; Kim et al, 2011; Rastogi et al, 2016), and 3T3-L1 pre-adipocytes (Neyrolles et al, 2006), but also with murine primary pre-adipocytes and mature adipocytes obtained from WAT (Agarwal et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In vitro experiments were conducted using murine 3T3-L1 mature adipocytes (Neyrolles et al, 2006; Kim et al, 2011; Rastogi et al, 2016), and 3T3-L1 pre-adipocytes (Neyrolles et al, 2006), but also with murine primary pre-adipocytes and mature adipocytes obtained from WAT (Agarwal et al, 2014). In immune-competent mice, intravenously and intra-nasally inoculated M. tuberculosis disseminates in WAT of visceral, subcutaneous, peri-renal and mesenteric adipose depots (Agarwal et al, 2014, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Mycobacterium canettii Infection of Adipose Tissues

Bouzid

Poncin

Weber

et al. 2017

Front. Cell. Infect. Microbiol.

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Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii, a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18–22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii (p = 0.02) and M. tuberculosis (p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis (p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii, it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

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Differential immune response of adipocytes to virulent and attenuated Mycobacterium tuberculosis

Cited by 20 publications

References 46 publications

Paracoccidioides brasiliensis induces secretion of IL-6 and IL-8 by lung epithelial cells. Modulation of host cytokine levels by fungal proteases

Paracoccidioides brasiliensis induces secretion of IL-6 and IL-8 by lung epithelial cells. Modulation of host cytokine levels by fungal proteases

Infection of human THP-1 cells with dormant Mycobacterium tuberculosis

Mycobacterium canettii Infection of Adipose Tissues

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