Impact of autophagic regulation on splenic red pulp macrophages during cerebral malarial infection

Sengupta, Anirban; Sarkar, Samrat; Keswani, Tarun; Mukherjee, Saikat; Ghosh, Soubhik; Bhattacharyya, Arindam

doi:10.1016/j.parint.2019.03.008

Cited by 14 publications

(9 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…pathogens, we posited that ARU may also promote MΦ-mediated clearance of P.b. Macrophages recognize malaria-infected RBCs through dangerassociated molecular patterns (DAMPs) and engulf them by phagocytosis, subsequently clearing them via autophagosome formation [22][23][24][25] . To test whether ARU contributes to clearance of P.b.-infected RBCs, we examined two markers, microtubuleassociated protein 1A/1B-light chain 3 (LC3), an autophagy/ autophagosome marker, and nitric oxide (NO), a marker for reactive oxygen species.…”

Section: Resultsmentioning

confidence: 99%

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

et al. 2021

View full text Add to dashboard Cite

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37−/− mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.

show abstract

Section: Resultsmentioning

confidence: 99%

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Clearing blood-borne pathogens is a hallmark feature of the spleen. In this secondary lymphoid organ, pDCs and red pulp macrophages efficiently cleared malaria parasites after boosting autophagy with rapamycin (67,68). The treatment enhanced antigen presentation in these cells and shifted the cytokine and chemokines profile in vivo which recruited effector cells into the spleen and enhanced T cell responses.…”

Section: Therapeutic Approaches Against Infections By Modulating Automentioning

confidence: 98%

Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Tao

Drexler

2020

Front. Immunol.

View full text Add to dashboard Cite

Innate immune cells are the "doorkeepers" in the immune system and are important for the initiation of protective vaccine responses against infection. Being an essential regulatory component of the immune system in these cells, autophagy not only mediates pathogen clearance and cytokine production, but also balances the immune response by preventing harmful overreaction. Interestingly, recent literature indicates that autophagy is positively or negatively regulating the innate immune response in a cell type-specific manner. Moreover, autophagy serves as a bridge between innate and adaptive immunity. It is involved in antigen presentation by delivering pathogen compounds to B and T cells, which is important for effective immune protection. Upon infection, autophagy can also be hijacked by some pathogens for replication or evade host immune responses. As a result, autophagy seems like a double-edged sword to the immune response, strongly depending on the cell types involved and infection models used. In this review, the dual role of autophagy in regulating the immune system will be highlighted in various infection models with particular focus on dendritic cells, monocytes/macrophages and neutrophils. Targeting autophagy in these cells as for therapeutic application or prophylactic vaccination will be discussed considering both roles of autophagy, the "angel" enhancing innate immune responses, antigen presentation, pathogen clearance and dampening inflammation or the "demon" enabling viral replication and degrading innate immune components. A better understanding of this dual potential will help to utilize autophagy in innate immune cells in order to optimize vaccines or treatments against infectious diseases.

show abstract

“…[14]. Autophagy cause the selection and display of peculiar antigens on class II MHC molecules for onward activation of the adaptive immunity [14,58]. Evidence shows that parasite antigens are engulfed through phagocytosis and further polished in class II MHC compartment (MIIC) which is acidic for presentation to CD4+ T cells [1].…”

Section: Atg Proteins Functionmentioning

confidence: 99%

“…There is further suspicion that ATG5 is likely to control the CD4 + T cell cytokine response in dendritic cells via processes different from both canonical autophagy and phagocytosis linked with LC3 machinery or response dependent on the Immune Related GTPase (IRG) [62]. Thus, it can be inferred that autophagic enhancement systematically trigger the infiltration of both neutrophil and helper CD4 T cells via chemokine regulation [58]. These results brings to light the importance of autophagy as a partner to immune responses against some parasites, including T. cruzi.…”

Section: Atg Proteins Functionmentioning

confidence: 99%

Autophagy in the control and pathogenesis of parasitic infections

et al. 2020

View full text Add to dashboard Cite

Background: Autophagy has a crucial role in the defense against parasites. The interplay existing between host autophagy and parasites has varied outcomes due to the kind of host cell and microorganism. The presence of autophagic compartments disrupt a significant number of pathogens and are further cleared by xenophagy in an autolysosome. Another section of pathogens have the capacity to outwit the autophagic pathway to their own advantage. Result: To comprehend the interaction between pathogens and the host cells, it is significant to distinguish between starvation-induced autophagy and other autophagic pathways. Subversion of host autophagy by parasites is likely due to differences in cellular pathways from those of 'classical' autophagy and that they are controlled by parasites in a peculiar way. In xenophagy clearance at the intracellular level, the pathogens are first ubiquitinated before autophagy receptors acknowledgement, followed by labeling with light chain 3 (LC3) protein. The LC3 in LC3-associated phagocytosis (LAP) is added directly into vacuole membrane and functions regardless of the ULK, an initiation complex. The activation of the ULK complex composed of ATG13, FIP200 and ATG101causes the initiation of host autophagic response. Again, the recognition of PAMPs by conserved PRRs marks the first line of defense against pathogens, involving Toll-like receptors (TLRs). These all important immune-related receptors have been reported recently to regulate autophagy. Conclusion: In this review, we sum up recent advances in autophagy to acknowledge and understand the interplay between host and parasites, focusing on target proteins for the design of therapeutic drugs. The target host proteins on the initiation of the ULK complex and PRRs-mediated recognition of PAMPs may provide strong potential for the design of therapeutic drugs against parasitic infections.

show abstract

Impact of autophagic regulation on splenic red pulp macrophages during cerebral malarial infection

Cited by 14 publications

References 43 publications

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Autophagy in the control and pathogenesis of parasitic infections

Contact Info

Product

Resources

About