The STAT pathway mediates late-phase immunity against Plasmodium in the mosquito Anopheles gambiae.
The STAT family of transcription factors activates expression of immune system genes in vertebrates. The ancestral STAT gene (AgSTAT-A) appears to have duplicated in the mosquito Anopheles gambiae, giving rise to a second intronless STAT gene (AgSTAT-B), which we show regulates AgSTAT-A expression in adult females. AgSTAT-A participates in the transcriptional activation of nitric oxide synthase (NOS) in response to bacterial and plasmodial infection. Activation of this pathway, however, is not essential for mosquitoes to survive a bacterial challenge. AgSTAT-A silencing reduces the number of early Plasmodium oocysts in the midgut, but nevertheless enhances the overall infection by increasing oocyst survival. Silencing of SOCS, a STAT suppressor, has the opposite effect, reducing Plasmodium infection by increasing NOS expression. Chemical inhibition of mosquito NOS activity after oocyte formation increases oocyte survival. Thus, the AgSTAT-A pathway mediates a late-phase antiplasmodial response that reduces oocyst survival in A. gambiae.
Gupta
Lalita
L
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892-8130, USA.
Molina-Cruz
Alvaro
A
Kumar
Sanjeev
S
Rodrigues
Janneth
J
Dixit
Rajnikant
R
Zamora
Rodolfo E
RE
Barillas-Mury
Carolina
C
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000469:parasitology*; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D006790:Host-Parasite Interactions; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D033661:Oocysts / Q000254:growth & development / Q000502:physiology; D010802:Phylogeny; D010961:Plasmodium / Q000254:growth & development* / Q000502:physiology; D050791:STAT Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D015398:Signal Transduction
D019476:Insect Proteins; D050791:STAT Transcription Factors; D019001:Nitric Oxide Synthase