Interpretive Summary: Alveolar macrophage functions during the transition phase to active immunity in calves
By: Jackie Walling
Bronchopneumonia is a common illness contracted in the first months of calves’ lives resulting in increased mortality. An article published in the September 2018 Issue of the Journal of Animal Science investigated the functions of alveolar macrophages in Holstein calves from aged three to six months, a time when the pulmonary immune system is in the process of maturing. Incidences of bronchopneumonia likely occur up to 5 months of age due to the time it takes to establish a sufficient immune system and instances of exaggerated cytotoxic responses to infections. Researchers focused on functions of phagocytosis, production of reactive oxygen species (ROS), classes of immunoglobulins, and cytokines related to lymphocyte response patterns Th1 (neutrophilic functions) and Th2 (particle agglutination of antigens).
Ten 1-week old bulls originating from San Paulo were removed from mothers to acclimate to research conditions. They were bottle fed until day 60 and officially weaned to a commercial ration and hay. Day 1 of the study commenced when the calves reached 3 months of age. Calves underwent clinical examinations daily, hemograms weekly, and the bronchoalveolar immune function was addressed during a winter and summer season of study. Each season contained 5 calves and functions were taken at seven different time points with two or three calves randomly sampled every 15 days. Bronchoalveolar lavage and blood serum quantified immunoglobulins. Through the process of flow cytometry, functions of phagocytosis and ROS production were identified based off of total bronchoalveolar cells and CD14+ bronchoalveolar cells. Real-time PCR evaluated cytokines IL-12, IL-10, and TNF-α.
Bronchoalveolar cells were compared to a category of CD14+ bronchoalveolar cells regarding functions of phagocytosis and ROS production. CD14+ bronchoalveolar cells showed statistically significant results while bronchoalveolar cells followed similar patterns, but to a lesser degree. CD14+ cells showed the highest activity at 120d. Phagocytosis for CD14+ showed an increase to day 120 as well, suggesting immaturity of the immune system with this direct relationship. In previous days, the CD14+ indicates ineffectiveness of the system being stimulated at 120d to maintain the health of the immune system by increasing its numbers. ROS production finally shows a big increase at 150d, which appears to be exaggerated. After 150d, all three parameters jostle around where cellular activity of CD14+ decreases but maturity is suggested because production of ROS is occurring simultaneously with phagocytosis at 180d. Maturity begins between 135 and 150d potentially stimulated by an exaggerated immune response around 150d.
IgA was the dominant immunoglobulin in the respiratory tract unaffected by age. IgG1 and IgG2 (related to Th2 and Th1 response respectively), were balanced until day 150 where IgG1 was prevalent over IgG2 before returning to equilibrium again at 180d. Blood serum showed a similar pattern. Cytokines IL-12 and TNF-α, associated with the Th1 response, stimulated B-lymphocytes to produce IgG2. Cytokines IL-10, associated with the Th2 response, caused lymphocytes to produce IgE causing production of IgG1. Th1 and Th2 profiles influenced each other until they balanced at 180d where ultimately a decrease in the IL-10 mRNA expression and an increase in the IL-12 and TNF-α mRNA expression was observed.
As one of the first studies to focus on the age of 3-6 months, it appears immune system maturity takes place during this time. By understanding the process, preventative measure against the contraction of bronchopneumonia could potentially be developed.
For the full article, visit the Journal of Animal Science.