Susceptibility to infectious diseases: Leishmania as a paradigm

J Infect Dis. 1999 Mar;179 Suppl 2:S305-8. doi: 10.1086/513843.


The diverse response of individuals within populations to infectious pathogens remains poorly understood, although genetic determinants undoubtedly contribute in substantial ways to the outcome of infection. In a mouse model of infection with the intramacrophage protozoan Leishmania major, susceptibility correlates both with aberrant helper T cell differentiation biased towards the production of interleukin 4 and with the presence of an endogenous CD4 T cell repertoire that recognizes an immunodominant parasite antigen with high frequency. In the setting of the particular ecological niche occupied by Leishmania, this combination of otherwise unrelated factors synergizes to result in exquisite susceptibility to this single pathogen, without seemingly compromising host defenses against other agents. Similar paradigms could underlie susceptibility to other pathogenic organisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan*
  • CD4-Positive T-Lymphocytes / immunology
  • Humans
  • Interleukin-4 / biosynthesis
  • Leishmania major / genetics
  • Leishmania major / immunology
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / etiology
  • Leishmaniasis, Cutaneous / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology


  • Antigens, Protozoan
  • Protozoan Proteins
  • LACK antigen, Leishmania
  • Interleukin-4