title: Gene-specific sex effects on eosinophil infiltration in leishmaniasis.
abstract: BACKGROUND
  Sex influences susceptibility to many infectious diseases, including some manifestations of leishmaniasis. The disease is caused by parasites that enter to the skin and can spread to the lymph nodes, spleen, liver, bone marrow, and sometimes lungs. Parasites induce host defenses including cell infiltration, leading to protective or ineffective inflammation. These responses are often influenced by host genotype and sex. We analyzed the role of sex in the impact of specific gene loci on eosinophil infiltration and its functional relevance.
  
  
  METHODS
  We studied the genetic control of infiltration of eosinophils into the inguinal lymph nodes after 8 weeks ofLeishmania majorinfection using mouse strains BALB/c, STS, and recombinant congenic strains CcS-1,-3,-4,-5,-7,-9,-11,-12,-15,-16,-18, and -20, each of which contains a different random set of 12.5% genes from the parental "donor" strain STS and 87.5% genes from the "background" strain BALB/c. Numbers of eosinophils were counted in hematoxylin-eosin-stained sections of the inguinal lymph nodes under a light microscope. Parasite load was determined using PCR-ELISA.
  
  
  RESULTS
  The lymph nodes of resistant STS and susceptible BALB/c mice contained very low and intermediate numbers of eosinophils, respectively. Unexpectedly, eosinophil infiltration in strain CcS-9 exceeded that in BALB/c and STS and was higher in males than in females. We searched for genes controlling high eosinophil infiltration in CcS-9 mice by linkage analysis in F2hybrids between BALB/c and CcS-9 and detected four loci controlling eosinophil numbers.Lmr14(chromosome 2) andLmr25(chromosome 5) operate independently from other genes (main effects).Lmr14functions only in males, the effect ofLmr25is sex independent.Lmr15(chromosome 11) andLmr26(chromosome 9) operate in cooperation (non-additive interaction) with each other. This interaction was significant in males only, but sex-marker interaction was not significant. Eosinophil infiltration was positively correlated with parasite load in lymph nodes of F2hybrids in males, but not in females.
  
  
  CONCLUSIONS
  We demonstrated a strong influence of sex on numbers of eosinophils in the lymph nodes afterL. majorinfection and present the first identification of sex-dependent autosomal loci controlling eosinophilic infiltration. The positive correlation between eosinophil infiltration and parasite load in males suggests that this sex-dependent eosinophilic infiltration reflects ineffective inflammation.
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Slapničková
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Volkova
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Čepičková
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kobets
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Matyáš
authors.initials: M
authors.lastname: Šíma
authors.affiliation: Faculty of Science, Charles University, 128 44 Prague, Czech Republic.
authors.forename: Milena
authors.initials: M
authors.lastname: Svobodová
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY 14263 USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Demant
authors.affiliation: Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Lipoldová
keywords: Eosinophil infiltration; Genetic control; Leishmania major; Mouse model; QTL; Sex influence