Increased early local immune responses and altered worm development in high-dose infections of mice susceptible to the filaria Litomosoides sigmodontis.
The relationship between the number of larvae inoculated and filarial infection outcome is an important fundamental and epidemiological issue. Our study was carried out with BALB/c mice infected with the filaria Litomosoides sigmodontis. For the first time, an immunological analysis of infection with various doses was studied in parallel with parasitological data. Mice were inoculated with 200, 60 or 25 infective larvae (third stage larvae, L3), and monitored over 80 days. At 60 h post-inoculation the immune response was stronger in the 200 L3 group than the 25 L3 group. Cells from lymph nodes draining the site of inoculation proliferated intensely and produced large amounts of IL-5 and IL-4. In the pleural cavity, leukocyte populations accumulated earlier and in larger quantities. IgG1, IL-4 and IL-10 serum concentrations were transiently higher. During the first 10 days the worm recovery rates were identical in all groups, but decreased thereafter in the 200 L3 group. In this group, the development of the worms was altered, with reduced lengths, diminished intra-uterine production of microfilariae and abnormalities of male copulatory organs. Whereas mice inoculated with 25 L3 became microfilaraemic, only one third reached patency in the 200 L3 group. However, detrimental effects of high numbers of worms are not seen in studies using different inoculation protocols. This suggests that the very early events determine subsequent immune response and infection outcome rather than competitive interactions between the worms.
Babayan
Simon
S
Parasitologie Comparée et Modèles expérimentaux associé à INSERM U567 et Ecole Pratique des Hautes Etudes, Muséum National d'Histoire Naturelle, 61 rue Buffon, 75213, Paris Cedex 05, France.
Attout
Tarik
T
Specht
Sabine
S
Hoerauf
Achim
A
Snounou
Georges
G
Rénia
Laurent
L
Korenaga
Masataka
M
Bain
Odile
O
Martin
Coralie
C
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology*; D005370:Filarioidea / Q000033:anatomy & histology / Q000254:growth & development* / Q000276:immunology* / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis / Q000097:blood; D007962:Leukocytes; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D035422:Pleural Cavity / Q000276:immunology; D013997:Time Factors
D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4