Deciphering the Role of Macrophage Subsets and Macrophage-Derived Factors During Arthrogenic Alphaviral Infection

View/ Open
Author(s)
Primary Supervisor
Mahalingam, Suresh
Other Supervisors
Herrero, Lara
Rulli, Nestor
Sheng, Kuo-Ching
Year published
2015
Metadata
Show full item recordAbstract
The current situation of global warming has a serious impact on the control of arthropod-borne infectious diseases. Climate change has led to an increase in conducive breeding habitats for mosquitoes. This change in climate has contributed to the widespread distribution of mosquito-transmitted arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV). RRV is currently endemic to Australia and Papua New Guinea, while CHIKV causes global outbreaks. The recent CHIKV outbreak in the Americas has taken the world by surprise and has affected more than 1 million individuals as of early 2015. To date, ...
View more >The current situation of global warming has a serious impact on the control of arthropod-borne infectious diseases. Climate change has led to an increase in conducive breeding habitats for mosquitoes. This change in climate has contributed to the widespread distribution of mosquito-transmitted arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV). RRV is currently endemic to Australia and Papua New Guinea, while CHIKV causes global outbreaks. The recent CHIKV outbreak in the Americas has taken the world by surprise and has affected more than 1 million individuals as of early 2015. To date, there are no specific therapeutics strategies available for the treatment of alphaviral diseases, largely due to the ill-defined innate immune responses elicited by these viruses. This thesis describes new insights into the alphavirus-elicited immune response at the cellular and molecular levels using in vitro, in vivo and ex vivo experimental approaches. In these studies, we identified the differential role of macrophages in modulating the RRV disease progression through an atypical IL-10-dependent M1/M2 polarisation of inflammatory monocytes. RRV-induced differentiation of M1 macrophages triggered the pathogenic inflammatory processes giving rise to the onset of disease, while M2 macrophages were shown to play a protective role.
View less >
View more >The current situation of global warming has a serious impact on the control of arthropod-borne infectious diseases. Climate change has led to an increase in conducive breeding habitats for mosquitoes. This change in climate has contributed to the widespread distribution of mosquito-transmitted arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV). RRV is currently endemic to Australia and Papua New Guinea, while CHIKV causes global outbreaks. The recent CHIKV outbreak in the Americas has taken the world by surprise and has affected more than 1 million individuals as of early 2015. To date, there are no specific therapeutics strategies available for the treatment of alphaviral diseases, largely due to the ill-defined innate immune responses elicited by these viruses. This thesis describes new insights into the alphavirus-elicited immune response at the cellular and molecular levels using in vitro, in vivo and ex vivo experimental approaches. In these studies, we identified the differential role of macrophages in modulating the RRV disease progression through an atypical IL-10-dependent M1/M2 polarisation of inflammatory monocytes. RRV-induced differentiation of M1 macrophages triggered the pathogenic inflammatory processes giving rise to the onset of disease, while M2 macrophages were shown to play a protective role.
View less >
Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
Institute for Glycomics
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Subject
Arthropod-borne infectious diseases
Ross River virus (RRV)
Chikungunya virus (CHIKV)
Global warming