scholarly journals A Dual Role for Macrophages in Modulating Lung Tissue Damage/Repair during L2 Toxocara canis Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 280 ◽  
Author(s):  
Berenice Faz-López ◽  
Héctor Mayoral-Reyes ◽  
Rogelio Hernández-Pando ◽  
Pablo Martínez-Labat ◽  
Derek M. McKay ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Tissue Damage ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Parasitic Infection ◽  
Toxocara Canis ◽  
Parasitic Infections ◽  
Lung Pathology ◽  
M2 Macrophages ◽  
Alternatively Activated Macrophages

Macrophages that are classically activated (M1) through the IFN-γ/STAT1 signaling pathway have a major role in mediating inflammation during microbial and parasitic infections. In some cases, unregulated inflammation induces tissue damage. In helminth infections, alternatively activated macrophages (M2), whose activation occurs mainly via the IL-4/STAT6 pathway, have a major role in mediating protection against excessive inflammation, and has been associated with both tissue repair and parasite clearance. During the lung migratory stage of Toxocara canis, the roles of M1 and M2 macrophages in tissue repair remain unknown. To assess this, we orally infected wild-type (WT) and STAT1 and STAT6-deficient mice (STAT1−/− and STAT6−/−) with L2 T. canis, and evaluated the role of M1 or M2 macrophages in lung pathology. The absence of STAT1 favored an M2 activation pattern with Arg1, FIZZ1, and Ym1 expression, which resulted in parasite resistance and lung tissue repair. In contrast, the absence of STAT6 induced M1 activation and iNOS expression, which helped control parasitic infection but generated increased inflammation and lung pathology. Next, macrophages were depleted by intratracheally inoculating mice with clodronate-loaded liposomes. We found a significant reduction in alveolar macrophages that was associated with higher lung pathology in both WT and STAT1−/− mice; in contrast, STAT6−/− mice receiving clodronate-liposomes displayed less tissue damage, indicating critical roles of both macrophage phenotypes in lung pathology and tissue repair. Therefore, a proper balance between inflammatory and anti-inflammatory responses during T. canis infection is necessary to limit lung pathology and favor lung healing.

scholarly journals Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation

2020 ◽  
Author(s):  
Ryan G. Snodgrass ◽  
Yvonne Benatzy ◽  
Tobias Schmid ◽  
Dmitry Namgaladze ◽  
Malwina Mainka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Repair ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Th2 Cytokines ◽  
Alternatively Activated Macrophages ◽  
Anti Inflammatory ◽  
Alternatively Activated

Abstract Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation and promote tissue repair. While alternatively activated macrophages (AAMs), also referred to as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute to the suppression of inflammatory responses and play a pivotal role in wound healing, contemporaneous exposure to apoptotic cells (ACs) potentiates the expression of anti-inflammatory and tissue repair genes. Given that liver X receptors (LXRs), which coordinate sterol metabolism and immune cell function, play an essential role in the clearance of ACs, we investigated whether LXR activation following engulfment of ACs selectively potentiates the expression of Th2 cytokine-dependent genes in primary human AAMs. We show that AC uptake simultaneously upregulates LXR-dependent, but suppresses SREBP-2-dependent gene expression in macrophages, which are both prevented by inhibiting Niemann–Pick C1 (NPC1)-mediated sterol transport from lysosomes. Concurrently, macrophages accumulate sterol biosynthetic intermediates desmosterol, lathosterol, lanosterol, and dihydrolanosterol but not cholesterol-derived oxysterols. Using global transcriptome analysis, we identify anti-inflammatory and proresolving genes including interleukin-1 receptor antagonist (IL1RN) and arachidonate 15-lipoxygenase (ALOX15) whose expression are selectively potentiated in macrophages upon concomitant exposure to ACs or LXR agonist T0901317 (T09) and Th2 cytokines. We show priming macrophages via LXR activation enhances the cellular capacity to synthesize inflammation-suppressing specialized proresolving mediator (SPM) precursors 15-HETE and 17-HDHA as well as resolvin D5. Silencing LXRα and LXRβ in macrophages attenuates the potentiation of ALOX15 expression by concomitant stimulation of ACs or T09 and IL-13. Collectively, we identify a previously unrecognized mechanism of regulation whereby LXR integrates AC uptake to selectively shape Th2-dependent gene expression in AAMs.

scholarly journals Signal Transducer and Activator of Transcription Factor 6 Signaling Contributes to Control Host Lung Pathology but Favors Susceptibility againstToxocara canisInfection

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Berenice Faz-López ◽  
Yadira Ledesma-Soto ◽  
Yolanda Romero-Sánchez ◽  
Elsa Calleja ◽  
Pablo Martínez-Labat ◽  
...  
Keyword(s):  
Toxocara Canis ◽  
Lung Pathology ◽  
Activated Macrophages ◽  
Wild Type ◽  
Gastrointestinal Helminths ◽  
Th2 Response ◽  
Alternatively Activated Macrophages ◽  
Severe Pathology ◽  
Alternatively Activated

UsingSTAT6−/−BALB/c mice, we have analyzed the role of STAT6-induced Th2 response in determining the outcome of experimental toxocariasis caused by embryonated eggs of the helminth parasiteToxocara canis. FollowingT. canisinfection wild-type BALB/c mice developed a strong Th2-like response, produced high levels of IgG1, IgE, and IL-4, recruited alternatively activated macrophages, and displayed a moderate pathology in the lungs; however, they harbored heavy parasite loads in different tissues. In contrast, similarly infectedSTAT6−/−BALB/c mice mounted a weak Th2-like response, did not recruit alternatively activated macrophages, displayed a severe pathology in the lungs, but efficiently controlledT. canisinfection. These findings demonstrate that Th2-like response induced via STAT6-mediated signaling pathway mediates susceptibility to larval stage ofT. canis. Furthermore, they also indicate that unlike most gastrointestinal helminths, immunity against larvae ofT. canisis not mediated by a Th2-dominant response.

scholarly journals DAMPening Inflammation by Modulating TLR Signalling

2010 ◽  
Vol 2010 ◽  
pp. 1-21 ◽  
Author(s):  
A. M. Piccinini ◽  
K. S. Midwood
Keyword(s):  
Immune System ◽  
Tissue Damage ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Feedback Loops ◽  
Inflammatory Gene Expression ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Tlr Signalling

Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.

scholarly journals STAT1-Dependent Recruitment of Ly6ChiCCR2+ Inflammatory Monocytes and M2 Macrophages in a Helminth Infection

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1287
Author(s):  
Mireya Becerra-Díaz ◽  
Yadira Ledesma-Soto ◽  
Jonadab E. Olguín ◽  
Angel Sánchez-Barrera ◽  
Mónica G. Mendoza-Rodríguez ◽  
...  
Keyword(s):  
Post Infection ◽  
Viral Infections ◽  
Helminth Infection ◽  
Parasitic Infections ◽  
M2 Macrophages ◽  
Monocytic Cells ◽  
Alternatively Activated Macrophages ◽  
Inflammatory Monocytes ◽  
Th2 Cytokine

Signal Transducer and Activator of Transcription (STAT) 1 signaling is critical for IFN-γ-mediated immune responses and resistance to protozoan and viral infections. However, its role in immunoregulation during helminth parasitic infections is not fully understood. Here, we used STAT1−/− mice to investigate the role of this transcription factor during a helminth infection caused by the cestode Taenia crassiceps and show that STAT1 is a central molecule favoring susceptibility to this infection. STAT1−/− mice displayed lower parasite burdens at 8 weeks post-infection compared to STAT1+/+ mice. STAT1 mediated the recruitment of inflammatory monocytes and the development of alternatively activated macrophages (M2) at the site of infection. The absence of STAT1 prevented the recruitment of CD11b+Ly6ChiLy6G− monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b+Ly6ChiLy6G− cells. Importantly, CD11b+Ly6ChiLy6G− cells highly expressed PDL-1 and suppressed T-cell proliferation elicited by anti-CD3 stimulation. PDL-1+ cells were mostly absent in STAT1−/− mice. Furthermore, only STAT1+/+ mice developed M2 macrophages at 8 weeks post-infection, although macrophages from both T. crassiceps-infected STAT1+/+ and STAT1−/− mice responded to IL-4 in vitro, and both groups of mice were able to produce the Th2 cytokine IL-13. This suggests that CD11b+CCR2+Ly6ChiLy6G− cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b+CCR2+Ly6ChiLy6G− cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.

M1/M2 Macrophages in Diabetic Nephropathy: Nrf2/HO-1 as Therapeutic Targets

2018 ◽  
Vol 24 (20) ◽  
pp. 2241-2249 ◽  
Author(s):  
Robert Clive Landis ◽  
Kim R. Quimby ◽  
Andre R. Greenidge
Keyword(s):  
Diabetic Nephropathy ◽  
Drug Targets ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Scavenger Receptor ◽  
Human Model ◽  
Related Factor ◽  
M2 Macrophages ◽  
Tissue Remodelling ◽  
Alternatively Activated Macrophages

The process of inflammation is orchestrated by macrophages, according to their state of differentiation: thus, classically activated (M1) macrophages initiate the process by elaborating proinflammatory cytokines and reactive oxygen species, whereas the latter phase is controlled by alternatively activated macrophages (M2) to resolve inflammation and promote tissue remodelling with the release of growth factors. In a simple human inflammatory response, such as acute crystal arthropathy, macrophages progress linearly through M1 and M2 phases; however, in chronic inflammatory responses, such as atherosclerosis and Diabetic Nephropathy (DN), both M1 and M2 macrophages may coexist, leading to persistent inflammation and fibrosis. A key macrophage receptor that regulates conversion from M1 to M2 is CD163, the hemoglobin scavenger receptor. Scavenging of hemoglobin:haptoglobin (Hb:Hp) complexes via CD163 leads to nuclear translocation of the transcription factor Nrf2 (NF-E2-related factor 2), upregulation of heme oxygenase (HO)-1 cytoprotective protein, and release of interleukin (IL)-10 anti-inflammatory cytokine; IL-10 is then linked in a positive feedback loop to further CD163 expression. The potency of this M1/M2 switching pathway is underscored by the fact that human Hp2 polymorphisms are associated with worsened clinical outcomes for diabetic complications, including DN. Parallel observations in animals show that HO-1 activation by hemin protects against DN in rodent models of diabetes. This review discusses the concept that Nrf2/HO-1 acts as a ‘therapeutic funnel’ through which a range of natural and synthetic anti-oxidants may drive M1 to M2 switching and improved kidney function in diabetes. We also discuss our observations on the evolution of M1/M2 phenotypes in a human model of wound healing which has presented intriguing potential drug targets for DN, such as eotaxin/CCR3.

What are Hidden Facts behind Intestinal Parasitic Infections in Ilam City?

2019 ◽  
Vol 19 (3) ◽  
pp. 284-287
Author(s):  
S. Viesy ◽  
J. Abdi ◽  
Z. Rezaei
Keyword(s):  
Public Health ◽  
Intestinal Parasites ◽  
Parasitic Infection ◽  
Public Health Education ◽  
Health Problems ◽  
Parasitic Infections ◽  
Blastocystis Hominis ◽  
Cross Sectional ◽  
Intestinal Parasitic Infections ◽  
Number Of Patients

Background: Intestinal parasitic infections are the one of the most common health problems in developing countries. Objective: A number of patients die annually due to complications caused by these parasites.Therefore, the aim of this study was to investigate the rate and type of parasitic infections, determine the factors affecting them in Ilam city and also provide strategies to prevent them.In this descriptive cross-sectional study conducted in one of the Ilam labs in 2016, 417 stool specimens were randomly collected. All specimens were examined using direct and ethanol formaldehyde.Suspect specimens were examined using Trichrom staining. Demographic information was also recorded in a questionnaire, and finally the results were analyzed using statistical software SPSS 20.The data were then compared with Chi-square test. Results: Out of the 417 patients examined, 59 (14.1%) were infected with intestinal parasites. The type of parasitic infection in 9.4% was Blastocystis hominis, 3.6% Entamoeba coli, 0.5% Entamoeba histolytica, 0.5% Giardia and 0.2% Trichomonas hominis. Conclusion: Despite the improvement of public health, parasitic infections are still considered as one of the health problems in the city of Ilam. Therefore, proper planning, public health education, raising the level of health in the area and the provision of safe drinking water are some of the ways to reduce parasitic infections in the region.

scholarly journals Application of Dendrimers for Treating Parasitic Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 343
Author(s):  
Veronica Folliero ◽  
Carla Zannella ◽  
Annalisa Chianese ◽  
Debora Stelitano ◽  
Annalisa Ambrosino ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Water Solubility ◽  
Parasitic Infection ◽  
Three Dimensional ◽  
Medical Knowledge ◽  
High Ratio ◽  
Molecular Volume ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Wide Range

Despite advances in medical knowledge, parasitic diseases remain a significant global health burden and their pharmacological treatment is often hampered by drug toxicity. Therefore, drug delivery systems may provide useful advantages when used in combination with conventional therapeutic compounds. Dendrimers are three-dimensional polymeric structures, characterized by a central core, branches and terminal functional groups. These nanostructures are known for their defined structure, great water solubility, biocompatibility and high encapsulation ability against a wide range of molecules. Furthermore, the high ratio between terminal groups and molecular volume render them a hopeful vector for drug delivery. These nanostructures offer several advantages compared to conventional drugs for the treatment of parasitic infection. Dendrimers deliver drugs to target sites with reduced dosage, solving side effects that occur with accepted marketed drugs. In recent years, extensive progress has been made towards the use of dendrimers for therapeutic, prophylactic and diagnostic purposes for the management of parasitic infections. The present review highlights the potential of several dendrimers in the management of parasitic diseases.

scholarly journals Skin Immunomodulation during Regeneration: Emerging New Targets

2021 ◽  
Vol 11 (2) ◽  
pp. 85
Author(s):  
Loubna Mazini ◽  
Luc Rochette ◽  
Yousra Hamdan ◽  
Gabriel Malka
Keyword(s):  
Cell Proliferation ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Skin Barrier ◽  
Adipose Derived Stem Cells ◽  
T And B Cells ◽  
Tumor Growth Factor ◽  
Anti Inflammatory ◽  
Skin Function ◽  
Epidermal Regeneration

Adipose-Derived Stem Cells (ADSC) are present within the hypodermis and are also expected to play a pivotal role in wound healing, immunomodulation, and rejuvenation activities. They orchestrate, through their exosome, the mechanisms associated to cell differentiation, proliferation, and cell migration by upregulating genes implicated in different functions including skin barrier, immunomodulation, cell proliferation, and epidermal regeneration. ADSCs directly interact with their microenvironment and specifically the immune cells, including macrophages and T and B cells, resulting in differential inflammatory and anti-inflammatory mechanisms impacting, in return, ADSCs microenvironment and thus skin function. These useful features of ADSCs are involved in tissue repair, where the required cell proliferation, angiogenesis, and anti-inflammatory responses should occur rapidly in damaged sites. Different pathways involved have been reported such as Growth Differentiation Factor-11 (GDF11), Tumor Growth Factor (TGF)-β, Metalloproteinase (MMP), microRNA, and inflammatory cytokines that might serve as specific biomarkers of their immunomodulating capacity. In this review, we try to highlight ADSCs’ network and explore the potential indicators of their immunomodulatory effect in skin regeneration and aging. Assessment of these biomarkers might be useful and should be considered when designing new clinical therapies using ADSCs or their specific exosomes focusing on their immunomodulation activity.

scholarly journals Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ricardo Louzada da Silva ◽  
Diana M. Elizondo ◽  
Nailah Z. D. Brandy ◽  
Naomi L. Haddock ◽  
Thomas A. Boddie ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Inflammatory Cytokine ◽  
Leishmania Donovani ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Bone Marrow Cells ◽  
Parasitic Infections ◽  
Inflammatory Factor ◽  
Immune Functions ◽  
Inflammatory Cytokine Production

AbstractMacrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

scholarly journals Prevalence and Correlates of Intestinal Parasites among Patients Admitted to Mirembe National Mental Health Hospital, Dodoma, Tanzania

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Azan A. Nyundo ◽  
David Z. Munisi ◽  
Ainory P. Gesase
Keyword(s):  
Neglected Tropical Diseases ◽  
Intestinal Parasites ◽  
Psychiatric Patients ◽  
Parasitic Infection ◽  
Parasitic Infections ◽  
Intestinal Parasitic Infection ◽  
Psychiatric Facility ◽  
Concentration Data ◽  
Cross Sectional ◽  
Stool Samples

Background. Neglected tropical diseases continue to be one of the leading causes of morbidity and mortality in the developing world. Psychiatric patients are among groups at risk for parasitic infection although control and monitoring programs largely overlook this population. This study aimed at determining prevalence and factors associated with intestinal parasitic infection among patients admitted to a psychiatric facility.Method. The study followed cross-sectional design; all the residing patients that met the inclusion criteria were included in the survey. Stool samples were collected and examined by direct wet preparation and formol-ether concentration. Data were analyzed with STATA version 12.1; Chi-square test was computed to determine the level of significance atpvalue < 0.05.Results.Of all 233 patients who returned the stool samples, 29 (12.45%) screened were positive for an intestinal parasite. There was no significant association between parasite carriage and age, sex, or duration of hospital stay.Conclusion. The study shows that intestinal parasitic infection is common among patients in a psychiatric facility and highlights that parasitic infections that enter through skin penetration may be a more common mode of transmission than the oral route. Furthermore, the study underscores the need for surveillance and intervention programs to control and manage these infections.

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