The O'Farrell lab at UCSF
Innate Immunity Research

The innate immune response is an ancient and phylogenetically widespread first line of defense against invading organisms. Drosophila is emerging as a potent tool for investigating innate immunity and identifying the genetic and molecular basis for innate immunity. Drosophila employ several different tactics to defend themselves against invading pathogens. Any potential pathogens must cross one or more epithelial barriers to gain access to the host.


Production of antimicrobial peptides is visualized in a section of the trachea (A), hemocytes (C) or fat body (D,E) in 3rd instar larvae expressing GFP under the control of the drosomycin promoter.
Invading pathogens can be destroyed by circulating macrophage-like cells, known as plasmatocytes, encapsulated by lamellocytes or destroyed by crystal cells. Drosophila also respond to infection with the production of antimicrobial peptides in a number of different tissues.

Expression of such peptides can be local in nature (panel A) or more systemic.

In the example shown in panel B a larvae has been exposed to a septic injury by pricking with a needle soaked in a bacterial pellet. A melanisation reaction occurs at the site of injury (dark spots) and the fat body, an organ analogous to the liver commences production of antimicrobial peptides. Systemic production of antimicrobial peptides in response to infection are illustrated in panels D and E. An additional element of the innate immune response in the phagocytic encapsulation and destruction of pathogens by circulating hemocytes. Hemocytes can also produce antimicrobial peptides (panel C).

Countless studies have indicated a role for nitric oxide (NO) in the immune response of a broad range of plants, invertebrates and vertebrates. It has been suggested that nitric oxide might function directly as a bactericidal agent or as a signaling molecule that activates other arms of the immune response. We are using the model organism Drosophila to explore these possibilities. Pharmacological manipulations of NO levels are being combined with analysis of known mutants in the innate immune response to determine to what extent NO contributes to innate immunity. As innate immunity is such a conserved and widespread process these studies can help illuminate our general understanding of immunity.

 

   Research  ·  People  ·  Publications  ·  Contact Us