@article{fdi:010048339, title = {{F}ine pathogen discrimination within the {APL}1 gene family protects {A}nopheles gambiae against human and rodent malaria species}, author = {{M}itri, {C}. and {J}acques, {J}. {C}. and {T}hiery, {I}. and {R}iehle, {M}. {M}. and {X}u, {J}. {N}. and {B}ischoff, {E}. and {M}orlais, {I}sabelle and {N}sango, {S}andrine and {V}ernick, {K}. {D}. and {B}ourgouin, {C}.}, editor = {}, language = {{ENG}}, abstract = {{G}enetically controlled resistance of {A}nopheles gambiae mosquitoes to {P}lasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the {P}lasmodium-{R}esistance {I}sland ({PRI}) of the {A}. gambiae genome. {T}he {APL}1 family of leucine-rich repeat ({LRR}) proteins was highlighted by candidate gene studies in the {PRI}, and is comprised of paralogs {APL}1{A}, {APL}1{B} and {APL}1{C} that share >= 50% amino acid identity. {H}ere, we present a functional analysis of the joint response of {APL}1 family members during mosquito infection with human and rodent {P}lasmodium species. {O}nly paralog {APL}1{A} protected {A}. gambiae against infection with the human malaria parasite {P}. falciparum from both the field population and in vitro culture. {I}n contrast, only paralog {APL}1{C} protected against the rodent malaria parasites {P}. berghei and {P}. yoelii. {W}e show that anti-{P}. falciparum protection is mediated by the {I}md/{R}el2 pathway, while protection against {P}. berghei infection was shown to require {T}oll/{R}el1 signaling. {F}urther, only the short {R}el2-{S} isoform and not the long {R}el2-{F} isoform of {R}el2 confers protection against {P}. falciparum. {P}rotection correlates with the transcriptional regulation of {APL}1{A} by {R}el2-{S} but not {R}el2-{F}, suggesting that the {R}el2-{S} anti-parasite phenotype results at least in part from its transcriptional control over {APL}1{A}. {T}hese results indicate that distinct members of the {APL}1 gene family display a mutually exclusive protective effect against different classes of {P}lasmodium parasites. {I}t appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. {I}t is known that insect innate immune pathways can distinguish between grossly different microbes such as {G}ram-positive bacteria, {G}ram-negative bacteria, or fungi, but the function of the {APL}1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between classes of closely related eukaryotic pathogens than has been previously recognized.}, keywords = {}, booktitle = {}, journal = {{P}lo{S} {P}athogens}, volume = {5}, numero = {9}, pages = {art. e1000576}, ISSN = {1553-7366}, year = {2009}, DOI = {10.1371/journal.ppat.1000576}, URL = {https://www.documentation.ird.fr/hor/fdi:010048339}, }