I am having a hard time finding literature reports on infection of C57Bl/6xBalb/c mice with Leishmania major. If I have an F1 generation of mice from C57Bl/6 and Balb/c, and infect them with L. major, would the disease outcome be more severe than the self-healing form observed in C57Bl/6, but not as bad as in Balb/c mice? In other words, would they develop some sort of "mixed" Th1/Th2 polarization?
You're assuming that the two "traits" (BALB/c and C57Bl/6) are co-dominant. There's no reason to assume this. It's certainly been a long time since I was involved with L, but my recollection is that C57, BALB and CBA had quite distinct responses to L major and L minor. I think this is one of those questions that could only be solved by an EXPERIMENT.....
However, before you do this - ask why do you want to do it? What is it about the response you feel is important to dissect in this way?
If you REALLY want to pull apart the various C57 and BALB components of the response, I suggest you first review the work of Edward Wakeland on C57 x BALB congnics in SLE
Good luck
G
Hi, Iris Janet,
Roberts et al. 1997 analyzed skin lesions development in F1 hybrids between BALB/c and C57BL/6 after L. major infection (see Figure 1 in the reference below). Skin lesions development in F1 was not intermediate, as Grant Gallagher assumes; F1 healed their lesions, but later than C57BL/6.
Roberts LJ, Baldwin TM, Curtis JM, Handman E, Foote SJ. Resistance to Leishmania major is linked to the H2 region on chromosome 17 and to chromosome 9. J Exp Med. 1997 May 5;185(9):1705-10.
PMID: 9151907
http://www.ncbi.nlm.nih.gov/pubmed/9151907
They did not analyzed cytokine expression in F1, however they tested cytokine expression in recombinant mice carrying susceptibility genes and found Th1/Th2 independent pathway of susceptibility control:
Elso CM, Roberts LJ, Smyth GK, Thomson RJ, Baldwin TM, Foote SJ, Handman E. Leishmaniasis host response loci (lmr1-3) modify disease severity through a Th1/Th2-independent pathway. Genes Immun. 2004 Mar;5(2):93-100.
PMID: 14668789
http://www.ncbi.nlm.nih.gov/pubmed/14668789
Elso C, Kumar B, Smyth G, Foote S, Handman E. Dissociation of disease susceptibility, inflammation and cytokine profile in lmr1/2 congenic mice infected with Leishmania major. Genes Immun. 2004 May;5(3):188-96.
http://www.ncbi.nlm.nih.gov/pubmed/14762398
Group, which analyzed F1 between BALB/c and Swiss mice found in F1 intermediate values of skin lesions and parasite numbers, however F1 mice did not differ from Swiss mice in IFNg levels:
Kiige SG, Mutiso JM, Laban LT, Khayeka-Wandabwa C, Anjili CO, Ingonga J, Gicheru MM. F₁ cross-breed between susceptible BALB/c and resistant Swiss mice infected with Leishmania major exhibit an intermediate phenotype for lesion sizes and type 1 cytokines but show low level of total IgG antibodies. Scand J Immunol. 2014 May;79(5):283-91. doi: 10.1111/sji.12159.
http://www.ncbi.nlm.nih.gov/pubmed/24498914
We worked with another genes combinations (recombinant congenic strains carrying 12.5% genes of resistant strain STS and 87.5% genes of susceptible strain BALB/c) and found several patterns of cytokine expression:
Lipoldová M, Svobodová M, Havelková H, Krulová M, Badalová J, Nohýnková E, Hart AA, Schlegel D, Volf P, Demant P. Mouse genetic model for clinical and immunological heterogeneity of leishmaniasis. Immunogenetics. 2002 Jun;54(3):174-83.
PMID: 12073146
http://www.ncbi.nlm.nih.gov/pubmed/12073146
https://www.researchgate.net/publication/11301971_Mouse_genetic_model_for_clinical_and_immunological_heterogeneity_of_leishmaniasis?ev=prf_pub
Genes controlling organ pathology only partly overlaps with genes controlling cytokine levels in serum:
Havelková H, Badalová J, Svobodová M, Vojtíková J, Kurey I, Vladimirov V, Demant P, Lipoldová M. Genetics of susceptibility to leishmaniasis in mice: four novel loci and functional heterogeneity of gene effects. Genes Immun. 2006 Apr;7(3):220-33.
PMID:16511555
http://www.ncbi.nlm.nih.gov/pubmed/16511555
https://www.researchgate.net/publication/7265431_Genetics_of_susceptibility_to_leishmaniasis_in_mice_four_novel_loci_and_functional_heterogeneity_of_gene_effects?ev=prf_pub
Lipoldová M, Demant P. Genetic susceptibility to infectious disease: lessons from mouse models of leishmaniasis. Nat Rev Genet. 2006 Apr;7(4):294-305.
PMID:16543933
http://www.ncbi.nlm.nih.gov/pubmed/16543933
https://www.researchgate.net/publication/7234796_Genetic_susceptibility_to_infectious_disease_lessons_from_mouse_models_of_leishmaniasis?ev=prf_pub
Thus, only part of Leishmania susceptibility genes is associated with cytokine control.
Good luck.
Marie
Article Mouse genetic model for clinical and immunological heterogen...
Article Genetics of susceptibility to leishmaniasis in mice: four no...
Article Genetic susceptibility to infectious disease: lessons from m...
- Badges
- Science topic
- Similar topics
- Biological Science
- Immunology