Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and Plasmodium.
The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism.
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130. Electronic address: amolina-cruz@niaid.nih.gov.
Alvaro
A
Molina-Cruz
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130.
Randall J
RJ
DeJong
Department of Microbiology, Immunology, and Pathology, Colorado State University, Ft. Collins, Colorado 80523.
Bradley
B
Charles
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130.
Lalita
L
Gupta
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130.
Sanjeev
S
Kumar
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130.
Giovanna
G
Jaramillo-Gutierrez
Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130.
Carolina
C
Barillas-Mury
D000818:Animals; D000852:Anopheles / Q000276:immunology* / Q000382:microbiology*; D000975:Antioxidants / Q000737:chemistry; D001419:Bacteria / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002468:Cell Physiological Phenomena; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000737:chemistry; D007113:Immunity, Innate; D010962:Plasmodium berghei / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species; D013997:Time Factors
D000975:Antioxidants; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase