The emergence of pathogenic TNF/iNOS producing dendritic cells (Tip-DCs) in a malaria model of acute respiratory distress syndrome (ARDS) is dependent on CCR4

Abstract

Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 ( PbN )-induced MA-ALI/ARDS model that resembles human disease and confirmed that lung CD4 + and CD8 + T cells predominantly expressed Tbet and IFN-γ. Surprisingly, we found that development of MA-ALI/ARDS was dependent on functional CCR4, known to mediate the recruitment of Th2 lymphocytes and regulatory T cells. However, in this Type 1 inflammation-ARDS model, CCR4 was not involved in the recruitment of T lymphocytes, but was required for the emergence of TNF-α/iNOS producing dendritic cells (Tip-DCs) in the lungs. In contrast, recruitment of Tip-DCs and development of MA-ALI/ARDS were not altered in CCR2 −/− mice. Importantly, we showed that NOS2 −/− mice are resistant to PbN -induced lung damage, indicating that reactive nitrogen species produced by Tip-DCs play an essential role in inducing MA-ARDS/ALI. Lastly, our experiments suggest that production of IFN-γ primarily by CD8 + T cells is required for inducing Tip-DCs differentiation in the lungs and the development of MA-ALI/ARDS model.

Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐ and immunohistochemical‐based evidences

“…Thus, HOCl, tyrosyl radical, NO 2 and MPO are collectively involved in the production of inflammatory cytokines (Aratani, ). It is well known that stressed condition is positively correlated with the inflammation, and TNF‐α is one of the extensively studied pro‐inflammatory cytokines having a well‐defined gonadal toxic profile in clinical and pre‐clinical findings (Galvão‐Filho et al, ; Veny, Virgen‐Slane, & Ware, ). In the current study, administration of CP 200, significant elevation in MPO expression and increased TNF‐α was observed in the testis and epididymis (Figure and Figure ).…”

“…related with the inflammation, and TNF-α is one of the extensively studied pro-inflammatory cytokines having a well-defined gonadal toxic profile in clinical and pre-clinical findings(Galvão-Filho et al, 2019;Veny, Virgen-Slane, & Ware, 2018). In the current study, administration of CP 200, significant elevation in MPO expression and increased TNF-α was observed in the testis and epididymis(Figure 2andFigure 3).…”

IL-6 During Influenza-Streptococcus pneumoniae Co-Infected Pneumonia—A Protector

“…Five-micrometer sections from fixed, paraffin-embedded whole lung were stained using hematoxylinand-eosin and examined by light microscopy. The scoring system was based on one that was previously report (27), briefly: 0 = no injury (apparently normal tissue); 1 = discrete and slight, when the lesion occupies <25% of the tissue; 2 = moderate when the lesion occupies 25-50% of the tissue; and 3 = intense, a severe injury with diffuse or focal inflammation around all structure of biopsy occupying more than 50% of the tissue.…”

Caspase-8 mediates inflammation and disease in rodent malaria

“…In our earlier studies, we found that MO-DCs are an important source of active caspase-1, IL-1β and have a pathogenic role in ECM and acute respiratory distress syndrome in malaria (MA-ARDS) models 18 , 44 , 49 . To address the importance of inflammatory caspases in ECM, RNA was extracted from MO-DCs (CD11b + F4/80 + CD11c + DC-Sign + MHC II + , purity >97%) highly purified from spleens of control and infected mice (Supplementary Fig.…”