scholarly journals Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

2019 ◽  
Author(s):  
Damiana Téllez-Martínez ◽  
Alexander Batista-Duharte ◽  
Vinicius Paschoalini Silva ◽  
Deivys Portuondo Fuentes ◽  
Lucas Souza Ferreira ◽  
...  
Keyword(s):  
Immune Response ◽  
Stress Response ◽  
Sporothrix Schenckii ◽  
Host Immune Response ◽  
Peritoneal Macrophages ◽  
Fungal Virulence ◽  
Functional Changes ◽  
Tnf Α ◽  
Intraperitoneal Infection ◽  
Adaptive Stress Response

ABSTRACTEnvironmental factors modify the physiology of microorganisms, allowing their survival in extreme conditions. However, the influence of chemical contaminants on fungal virulence has been little studied. Sporotrichosis is an emergent fungal disease caused bySporothrix schenckii,a soil-inhabiting fungus that has been found in polluted environments. Here, we evaluated the adaptive stress response ofS. schenckiiinduced by toluene, a key soil contaminant. The effect on fungal virulence and host immune response was also assessed. The fungus survived up to 0.10% toluene in liquid medium. Greater production of melanosomes and enhanced activity superoxide dismutase, associated to increased tolerance to H2O2were observed in toluene-exposed fungi. Intraperitoneal infection of mice withS. schenckiitreated with either 0, 0.01 or 0.1% of toluene, resulted in greater fungal burden at day 7 post-infection in spleen and liver in the groups infected with fungus treated with toluene 0.1%. A higher production of Il-1β, TNF-α, IL-10 and nitric oxyde by peritoneal macrophages and IFNγ, IL-4 and IL-17 by splenocytes was also observed in that group. Our findings showed that morphological and functional changes induced by toluene leads to increasedS. schenckiivirulence and antifungal host immune response in our model.

scholarly journals Failure To Recruit Anti-Inflammatory CD103+Dendritic Cells and a Diminished CD4+Foxp3+Regulatory T Cell Pool in Mice That Display Excessive Lung Inflammation and Increased Susceptibility to Mycobacterium tuberculosis

2012 ◽  
Vol 80 (3) ◽  
pp. 1128-1139 ◽  
Author(s):  
Chaniya Leepiyasakulchai ◽  
Lech Ignatowicz ◽  
Andrzej Pawlowski ◽  
Gunilla Källenius ◽  
Markus Sköld
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Bacterial Growth ◽  
Lung Inflammation ◽  
Chronic Infection ◽  
Host Immune Response ◽  
Content Type ◽  
Tnf Α

Susceptibility toMycobacterium tuberculosisis characterized by excessive lung inflammation, tissue damage, and failure to control bacterial growth. To increase our understanding of mechanisms that may regulate the host immune response in the lungs, we characterized dendritic cells expressing CD103 (αEintegrin) (αE-DCs) and CD4+Foxp3+regulatory T (Treg) cells duringM. tuberculosisinfection. In resistant C57BL/6 and BALB/c mice, the number of lung αE-DCs increased dramatically duringM. tuberculosisinfection. In contrast, highly susceptible DBA/2 mice failed to recruit αE-DCs even during chronic infection. Even though tumor necrosis factor alpha (TNF-α) is produced by multiple DCs and macrophage subsets and is required for control of bacterial growth, αE-DCs remained TNF-α negative. Instead, αE-DCs contained a high number of transforming growth factor beta-producing cells in infected mice. Further, we show that Tregcells in C57BL/6 and DBA/2 mice induce gamma interferon during pulmonary tuberculosis. In contrast to resistant mice, the Tregcell population was diminished in the lungs, but not in the draining pulmonary lymph nodes (PLN), of highly susceptible mice during chronic infection. Tregcells have been reported to inhibitM. tuberculosis-specific T cell immunity, leading to increased bacterial growth. Still, despite the reduced number of lung Tregcells in DBA/2 mice, the bacterial load in the lungs was increased compared to resistant animals. Our results show that αE-DCs and Tregcells that may regulate the host immune response are increased inM. tuberculosis-infected lungs of resistant mice but diminished in infected lungs of susceptible mice.

scholarly journals Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingying Lei ◽  
Xiaojian Cao ◽  
Weize Xu ◽  
Bing Yang ◽  
Yangyang Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Host Cell ◽  
Host Immune Response ◽  
Secreted Proteins ◽  
Cell Immune Response ◽  
Term Survival ◽  
Knock Down ◽  
Tnf Α

Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival.

scholarly journals Disruption of TNF-α/TNFR1 Function in Resident Skin Cells Impairs Host Immune Response against Cutaneous Vaccinia Virus Infection

2012 ◽  
Vol 132 (5) ◽  
pp. 1425-1434 ◽  
Author(s):  
Tian Tian ◽  
Krista Dubin ◽  
Qiushuang Jin ◽  
Ali Qureshi ◽  
Sandra L. King ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Vaccinia Virus ◽  
Host Immune Response ◽  
Skin Cells ◽  
Vaccinia Virus Infection ◽  
Tnf Α

scholarly journals Modulation of Cell Death byM. tuberculosisas a Strategy for Pathogen Survival

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Markos Abebe ◽  
Louise Kim ◽  
Graham Rook ◽  
Abraham Aseffa ◽  
Liya Wassie ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Host Immune Response ◽  
Extrinsic Pathway ◽  
Monocytic Cells ◽  
Tnf Α ◽  
Pathogen Survival ◽  
Infected Cells ◽  
In Cells

It has been clearly demonstrated thatin vitro, virulentM. tuberculosiscan favor necrosis over apoptosis in infected macrophages, and this has been suggested as a mechanism for evading the host immune response. We recently reported that an effect consistent with this hypothesis could be observed in cells from the blood of TB patients, and in this paper, we review what is known about evasion strategies employed byM. tuberculosisand in particular consider the possible interaction of the apoptosis-inhibiting effects ofM. tuberculosisinfection with another factor (IL-4) whose expression is thought to play a role in the failure to controlM. tuberculosisinfection. It has been noted that IL-4 may exacerbate TNF-α-induced pathology, though the mechanism remains unexplained. Since pathology in TB typically involves inflammatory aggregates around infected cells, where TNF-α plays an important role, we predicted that IL-4 would inhibit the ability of cells to removeM. tuberculosisby apoptosis of infected cells, through the extrinsic pathway, which is activated by TNF-α. Infection of human monocytic cells with mycobacteriain vitro, in the presence of IL-4, appears to promote necrosis over apoptosis in infected cells—a finding consistent with its suggested role as a factor in pathology duringM. tuberculosisinfection.

scholarly journals Paracoccin overexpression in Paracoccidioides brasiliensis reveals the influence of chitin hydrolysis on fungal virulence and host immune response

2019 ◽  
Author(s):  
Relber Aguiar Gonçales ◽  
Vanessa Cristina Silva Vieira ◽  
Rafael Ricci-Azevedo ◽  
Fabrício Freitas Fernandes ◽  
Sandra Maria de Oliveira Thomaz ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Response ◽  
Paracoccidioides Brasiliensis ◽  
In Vitro Assays ◽  
Significant Advance ◽  
Fungal Virulence ◽  
Tnf Α ◽  
Chitin Hydrolysis ◽  
Yeast Genes

ABSTRACTParacoccidioides brasiliensis and P. lutzii, etiological agents of paracoccidioidomycosis (PCM), develop as mycelia at 25-30 °C and as yeast at 35-37 °C. Only a few Paracoccidioides spp. proteins are well characterized. Thus, we studied paracoccin (PCN) from P. brasiliensis, its role in the fungus biology, and its relationship with the host innate immune cells. Cloning and heterologous expression analysis revealed its lectin, enzymatic, and immunomodulatory properties. Recently, we employed a system based on Agrobacterium tumefaciens-mediated transformation to manipulate P. brasiliensis yeast genes to obtain clones knocked-down for PCN, which after all, are unable to transit from yeast to mycelium forms, causing a mild pulmonary disease. Herein, we generate P. brasiliensis overexpressing PCN (ov-PCN). To date, it was not explored the overexpressing of endogenous components in Paracoccidioides spp. Therefore, we investigate the role of PCN in fungal biology and pathogenesis. Augmented levels of PCN mRNA and protein, and N-acetylglucosaminidase activity confirmed PCN overexpression in ov-PCN of P. brasiliensis yeasts. Interestingly, PCN overexpression did not affect the yeasts’ growth or viability and favored cell separation. The ov-PCN clones transitioned faster to the mycelium form than the wt-PCN yeasts. Concerning infection, while most of mice infected with the wt-yeasts (90%) survive at least until the 70th day, all mice infected with ov-PCN yeasts were already died at the 35th day post-infection. In vitro assays showed that ov-PCN were more susceptible to phagocytosis by macrophages. Finally, it was verified that the chitin particles isolated from the ov-PCN cells were smaller than those obtained from the wt-PCN yeasts. Macrophages stimulated with the chitin isolated from ov-PCN produce IL-10, whereas the particles with a wider size range harvested from wt-PCN yeasts induced TNF-α and IL-1β secretion. The anti-inflammatory microenvironment from macrophage stimulation with small chitin particles hampers the development of a protective immune response against the fungus. We postulated that the high grade of chitin cleavage, as the results of augmented PCN expression, favors pathogenesis following P. brasiliensis infection. Thus, PCN is a relevant virulence fungal factor.AUTHOR SUMMARYParacoccidioides spp. are pathogenic fungi that cause paracoccidioidomycosis (PCM) in humans, the main deep mycosis of Latin America. Recently, by knocking down the paracoccin gene, our group showed that this lectin is necessary for the morphological transition from yeast to hyphae, and that this decrease results in low P. brasiliensis virulence. Here, after overexpress PCN, we revealed the importance of the yeast chitin hydrolysis to the host response. Infection of mice with ov-PCN yeasts causes severe lung disease compared to moderate disease caused by wt-PCN yeasts. The release of smaller chitin particles was as a result of an accelerated chitin hydrolysis provided by ov-PCN yeasts. Interestingly, these smallest chitin particles are able to modulate host response by increasing IL-10 in the meantime that decrease TNF-α secretion, thus hampering Th1 immune response that is crucial in the fight against this fungi. These findings represent a significant advance in the knowledge about the role of PCN chitinase in P. brasiliensis.

scholarly journals Recombinant Guinea Pig Tumor Necrosis Factor Alpha Stimulates the Expression of Interleukin-12 and the Inhibition of Mycobacterium tuberculosis Growth in Macrophages

2005 ◽  
Vol 73 (3) ◽  
pp. 1367-1376 ◽  
Author(s):  
Hyosun Cho ◽  
Todd M. Lasco ◽  
Shannon Sedberry Allen ◽  
Teizo Yoshimura ◽  
David N. McMurray
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis ◽  
Peritoneal Macrophages ◽  
Interleukin 12 ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) plays an important role in the host immune response to infection with the intracellular pathogen Mycobacterium tuberculosis. It is essential for the formation of protective tuberculous granulomas and regulates the expression of other cytokines which contribute to a protective immune response. Interleukin-12 (IL-12) is known to promote a Th1 response, which is essential for antimycobacterial resistance. Recombinant guinea pig TNF-α (rgpTNF-α) protein (17 kDa) was purified, and its bioactivity was confirmed by its cytotoxicity for L929 fibroblasts. High titers of polyclonal anti-gpTNF-α antibody were obtained by immunization of rabbits. Resident alveolar and peritoneal macrophages were isolated from guinea pigs and infected with either the H37Ra or H37Rv strain of M. tuberculosis. The mRNA levels for TNF-α and IL-12 p40 were measured using real-time PCR. IL-12 p40 mRNA was up-regulated in a dose-dependent manner by rgpTNF-α alone. In infected macrophages, a lower dose of rgpTNF-α intensified the mRNA levels of TNF-α and IL-12 p40. However, higher doses of rgpTNF-α suppressed TNF-α and IL-12 p40 mRNA. The antimycobacterial activity of macrophages was assessed by metabolic labeling of M. tuberculosis with [3H]uracil. Resident alveolar and peritoneal macrophages treated with anti-gpTNF-α antibody to block endogenous TNF-α exhibited increased intracellular mycobacterial growth. These data suggest that the dose of TNF-α is crucial to the stimulation of optimal expression of protective cytokines and that TNF-α contributes to the control of mycobacterial replication to promote host resistance against M. tuberculosis.

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