Article| Volume 80, ISSUE 8, P1767-1775, August 1997

Genetic Association Between Parameters of Innate Immunity and Measures of Mastitis in Periparturient Holstein Cattle1

      This paper is only available as a PDF. To read, Please Download here.


      Relationships between genetic measures of mastitis (somatic cell score, score for clinical mastitis, and scores for IMI with major or minor pathogens) and immunological parameters (physiological and molecular markers) were examined for periparturient Holstein cows. Physiological markers included 11 in vitro immunological assays. Molecular markers included the second exon of the DRB3 locus of the bovine major histocompatibility complex, the IgG2 isotype genotype, and the CD18 genotype (the locus responsible for bovine leukocyte adhesion deficiency). A gene substitution model was used to estimate the additive genetic effects of alleles of the three molecular markers on estimated breeding value (EBV) for mastitis measures. Pearson correlation coefficients between EBV for immunological assays and EBV for mastitis measures were computed. Molecular markers explained up to 40% of the variation in EBV for measures of mastitis. The presence of allele DRB3.2*16 was associated with higher EBV for SCS. Allele DRB3.2*8 was associated with increased EBV for clinical mastitis, as was the IgG2b allele and the normal CD18 allele. Alleles DRB3.2*11, *23, IgG2a, and the recessive allele for bovine leukocyte adhesion deficiency were associated with decreased clinical mastitis. A positive genetic association was found between allele DRB3.2*24 and EBV for IMI by major pathogens and between DRB3.2*3 and IMI by minor pathogens. Several correlations between EBV for immunological assays and EBV for mastitis measures were significantly different from 0. Cows with low EBV for SCS tended to have neutrophils that had greater functional ability at maximal immunosuppression, low serum IgG1, and high numbers of circulating mononuclear cells. Immunological parameters, including physiological and molecular markers, are useful aids to understand the genetics of resistance to mastitis.

      Key words

      Abbreviation key:

      BLAD (bovine leukocyte adhesion deficiency), BoLA (bovine major histocompatibility complex), CM (clinical mastitis), IR (immune response), MHC (major histocompatibility complex), RFLP (restriction fragment length polymorphism)


        • Aarestrup F.M.
        • Jensen N.E.
        • Østergård H.
        Analysis of associations between major histocompatibility complex (BoLA) class I haplotypes and subclinical mastitis of dairy cows.
        J. Dairy Sci. 1995; 78: 1684
        • Blakeslee D.
        • Butler J.E.
        • Stone W.H.
        Serum antigens of cattle II. Immunogenetics of two immunoglobulin allotypes.
        J. Immunol. 1971; 107: 227
        • Boettcher P.J.
        • Hansen L.B.
        • Van Raden P.M.
        • Ernst C.A.
        Genetic evaluation of Holstein bulls for somatic cells in milk of daughters.
        J. Dairy Sci. 1992; 75: 1127
        • Butler J.E.
        Bovine immunoglobulins: an augmented review.
        Vet. Immunol. Immunopathol. 1983; 4: 43
        • Cai T.-Q.
        • Weston P.G.
        • Lund L.A.
        • Brodie B.
        • McKenna D.J.
        • Wagner W.C.
        Association between neutrophil functions and periparturient disorders in cows.
        Am. J. Vet. Res. 1994; 55: 934
        • Detilleux J.C.
        • Kehrli Jr, M.E.
        • Freeman A.E.
        • Fox L.K.
        • Kelley D.H.
        Mastitis of periparturient Holstein cattle: a phenotypic and genetic study.
        J. Dairy Sci. 1995; 78: 2285
        • Detilleux J.C.
        • Kehrli Jr, M.E.
        • Stabel J.R.
        • Freeman A.E.
        • Kelley D.H.
        Study of immunological dysfunction in periparturient Holstein cattle selected for high and average milk production.
        Vet. Immunol. Immunopathol. 1995; 44: 251
        • Detilleux J.C.
        • Koehler K.J.
        • Freeman A.E.
        • Kehrli Jr, M.E.
        • Kelley D.H.
        Immunological parameters of periparturient Holstein cattle: genetic variation.
        J. Dairy Sci. 1994; 77: 2640
        • Dietz A.B.
        • Cohen N.D.
        • Timms L.
        • Kehrli Jr, M.E.
        Bovine lymphocyte antigen Class II alleles as risk factors for high somatic cell counts in milk of lactating dairy cows.
        J. Dairy Sci. 1997; 80: 406
        • Dietz A.B.
        • Detilleux J.C.
        • Freeman A.E.
        • Kelley D.H.
        • Stabel J.R.
        • Kehrli Jr, M.E.
        Genetic association of bovine lymphocyte antigen DRB3 alleles with immunological traits of Holstein cattle.
        J. Dairy Sci. 1997; 80: 400
        • Gilbert R.O.
        • Rebhun W.C.
        • Kim C.A.
        • Kehrli Jr, M.E.
        • Shuster D.E.
        • Ackermann M.R.
        Clinical manifestations of leukocyte adhesion deficiency in cattle: 14 cases (1977–1991).
        J. AVMA. 1993; 202: 445
        • Hagemoser W.A.
        • Roth J.A.
        • Löfstedt J.
        • Fagerland J.A.
        Granulocytopathy in a Holstein heifer.
        J. AVMA. 1983; 183: 1093
        • Henderson C.R.
        Theoretical basis and computational methods for a number of different animal models.
        J. Dairy Sci. 1988; 71: 1
        • Heyermann H.
        • Butler J.E.
        • Frangione B.
        The heterogeneity of bovine IgG2—V. Differences in the primary structure of bovine IgG2 allotypes.
        Mol. Immunol. 1992; 29: 1147
        • Heyneman R.
        • Burvenich C.
        • Vercauteren R.
        Interaction between the respiratory burst activity of neutrophil leukocytes and experimentally induced Escherichia coli mastitis in cows.
        J. Dairy Sci. 1990; 73: 985
        • Hill A.W.
        Factors influencing the outcome of Escherichia coli mastitis in the dairy cows.
        Res. Vet. Sci. 1981; 31: 107
        • Ishikawa H.
        Observation of lymphocyte function in perinatal cows and neonatal calves.
        Jpn. J. Vet. Sci. 1987; 49: 469
        • Jain N.C.
        • Schalm O.W.
        • Carroll E.J.
        • Lasmanis J.
        Experimental mastitis in leukopenic cows: immunologically induced neutropenia and response to intramammary inoculation of Aerobacter aerogenes.
        Am. J. Vet. Res. 1968; 29: 2089
        • Kacskovics I.
        • Butler J.E.
        The heterogeneity of bovine IgG2—VIII. The complete cDNA sequence of bovine IgG2a (A2) and IgG1.
        Mol. Immunol. 1996; 33: 189
        • Kehrli Jr, M.E.
        • Nonnecke B.J.
        • Roth J.A.
        Alterations in bovine peripheral blood neutrophil function during the periparturient period.
        Am. J. Vet. Res. 1989; 50: 207
        • Kehrli Jr, M.E.
        • Schmalstieg F.C.
        • Anderson D.C.
        • Van Der Maaten M.J.
        • Hughes B.J.
        • Ackermann M.R.
        • Wilhelmsen C.L.
        • Brown G.B.
        • Stevens M.G.
        • Whetstone C.A.
        Molecular definition of the bovine granulocytopathy syndrome: identification of deficiency of the Mac-1 (CD11b/CD18) glycoprotein.
        Am. J. Vet. Res. 1990; 51: 1826
        • Kehrli Jr, M.E.
        • Weigel K.A.
        • Freeman A.E.
        • Thurston J.R.
        • Kelley D.H.
        Bovine sire effects on daughters’ in vitro blood neutrophil functions, lymphocyte blastogenesis, serum complement and conglutinin levels.
        Vet. Immunol. Immunopathol. 1991; 27: 303
        • Lie O.
        Genetic approach to mastitis control.
        Kiel. Milchwirtsch. Forschungsber. 1985; 37: 487
        • Lundén A.
        • Sigurdardóttir S.
        • Edfors-lilja I.
        • Danell B.
        • Rendel J.
        • Andersson L.
        The relationship between bovine major histocompatibility complex class II polymorphism and disease studied by use of bull breeding values.
        Anim. Genet. 1990; 21: 221
        • Nagahata H.
        • Makino S.
        • Takeda S.
        • Takahashi H.
        • Noda H.
        Assessment of neutrophil function in the dairy cow during the perinatal period.
        J. Vet. Med. Ser. B. 1988; 35: 747
        • Østergård H.
        • Kristensen B.
        • Andersen S.
        Investigations in farm animals of associations between the MHC system and disease resistance and fertility.
        Livest. Prod. Sci. 1989; 22: 49
        • Saad A.M.
        • Concha C.
        • Åström G.
        Alterations in neutrophil phagocytosis and lymphocyte blastogenesis in dairy cows around parturition.
        J. Vet. Med. Ser. B. 1989; 36: 337
      1. SAS® User's Guide: Statistics, Version 6 Edition. 1989. SAS Inst., Inc., Cary, NC.

        • Schalm O.W.
        • Lasmanis J.
        • Carroll E.J.
        Significance of leukocytic infiltration into the milk in experimental Streptococcus agalactiae mastitis in cattle.
        Am. J. Vet. Res. 1966; 27: 1537
        • Schalm O.W.
        • Ziv-Silberman G.
        Reactions following intramammary infusion of E. coli endotoxin.
        Vet. Rec. 1968; 82: 100
        • Shanks R.D.
        • Freeman A.E.
        • Dickinson F.N.
        Postpartum distribution of costs and disorders of health.
        J. Dairy Sci. 1981; 64: 683
        • Shuster D.E.
        • Kehrli Jr, M.E.
        • Ackermann M.R.
        • Gilbert R.O.
        Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 9225
        • Spooner R.L.
        • Morgan A.L.G.
        • Sales D.
        • Simpson S.P.
        • Solbu H.
        • Lie O.
        MHC associations with mastitis.
        Anim. Genet. 1988; 19: 57
        • Springer T.A.
        Adhesion receptors of the immune system.
        Nature (Lond.). 1989; 346: 425
        • Takahashi K.
        • Miyagawa K.
        • Abe S.
        • Kurosawa T.
        • Sonoda M.
        • Nakade T.
        • Nagahata H.
        • Noda H.
        • Chihaya Y.
        • Isogai E.
        Bovine granulocytopathy syndrome of Holstein-Friesian calves and heifers.
        Jpn. J. Vet. Sci. 1987; 49: 733
        • van Eijk M.J.T.
        • Stewart-Haynes J.A.
        • Lewin H.A.
        Extensive polymorphism of the BoLA-DRβ3 gene distinguished by PCR-RFLP.
        Anim. Genet. 1992; 23: 483
        • Weigel K.A.
        • Freeman A.E.
        • Kehrli Jr, M.E.
        • Thurston J.R.
        • Stear M.J.
        • Kelley D.H.
        Association of class I bovine lymphocyte antigen complex alleles with health and production traits in dairy cattle.
        J. Dairy Sci. 1990; 73: 2538
        • Williams M.R.
        • Hibbitt K.G.
        • Field T.R.
        • Bunch K.J.
        Further studies on the variation among cows, bulls and calves in the ability of their blood polymorphonuclear leukocytes to kill Staphylococcus aureus.
        Br. Vet. J. 1984; 140: 307