Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission

Ren, Yan; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Zhang, Shujun

doi:10.21775/cimb.021.021

Cited by 13 publications

(7 citation statements)

References 110 publications

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“…Macrophages have an essential role in the control of Mtb infection and paradoxically, also constitute the niche replication of mycobacteria [27,45]. Depending on the variability in the quality and quantity of cytokines produced during Mtb infection, macrophages can polarize to different cell types.…”

Section: Discussionmentioning

confidence: 99%

“…IL-10 and TGF-β) and are permissive for Mtb proliferation [46,47]. As Mtb promotes cell differentiation towards an M2 anti-in ammatory pro le [45], the modulation in the activity and phenotype of macrophages represents one of the potential approaches for host-directed immunotherapy against TB. The impact of DHEA on Mtb-infected THP-1 cells was previously studied, revealing that this particular hormone did not exhibit a reduction in bacterial burden, nor did it alter the secretion of cytokines by macrophages.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis

Vecchione,

Barrios-Payán,

Mata-Espinosa

et al. 2024

Preprint

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Anti-tuberculous therapy successfully eradicates the infection, but it is long-lasting and impose the use of multiple drugs. Therefore, it is required to develop additional immunotherapy approaches to protect and manage human tuberculosis. In this study, we examined the properties of 7-oxo- dehydroepiandrosterone (7-oxo-DHEA), a DHEA-derivative hormone, through both in vitro and in vivo settings for M. tuberculosis (Mtb) infection. Firstly, we observed that 7-oxo-DHEA exhibited a bacteriostatic effect over Mtb growth. Furthermore, in an in vitro model of infection, 7-oxo-DHEA improved the killing of Mtb by human and murine macrophages and reduced the levels of anti-inflammatory cytokines secretion. Remarkably, 7-oxo-DHEA treatment moderated Mtb growth and lung injury during the progressive phase of TB disease in mice. Our findings demonstrate that this compound enhances immune responses, resulting in a more favorable profile for mycobacteria control. Further investigations are required to explore the potential use of 7-oxo-DHEA as a novel adjunctive host-directed treatment in the context of pulmonary tuberculosis disease, constraining Mtb infection and preventing severe lung injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis

Vecchione,

Barrios-Payán,

Mata-Espinosa

et al. 2024

Preprint

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“…Studies have shown that these pathogenic microorganisms employ several evasion mechanisms to suppress pro-inflammatory response and activate MϕM2 in the host cells [26,28].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Quaresma,

de Aguiar Valentim,

de Sousa

et al. 2023

Pathogens

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Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

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“…Studies have shown that these pathogenic microorganisms employ several evasion mechanisms to suppress pro-inflammatory response and activate MφM2 in the host cells [28,26].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Quaresma¹,

Valentin²,

Sousa³

et al. 2023

Preprint

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Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with Leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. We performed simultaneous multiple immunostaining using monoclonal antibodies specific for inducible nitric oxide synthase (iNOS), IL-6, IL-10, IL-13, TNF-α, TGF-β, FGFb, CD163, CD68, arginase-1, MRP8, and MMP7. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p &lt; 0.0001), Borderline (1.6 ± 0.4, p &lt; 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p &lt; 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p &lt; 0.0001), Borderline (1.3 ± 0.2, p &lt; 0.0001), and TT (3.2 ± 0.7, p &lt; 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p &lt; 0.0001), Borderline (1.2 ± 0.2, p &lt; 0.0001), and TT (2.6 ± 0.7, p &lt; 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2×TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

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Immune Evasion Strategies of Pathogens in Macrophages: the Potential for Limiting Pathogen Transmission

Cited by 13 publications

References 110 publications

Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis

Therapeutic potential of 7-oxo-DHEA as an adjunctive host-directed therapy for pulmonary tuberculosis

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions

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