Pertussis: infection, vaccination and gene polymorphisms

Pertussis or whooping cough is a human respiratory tract infection and a vaccine-preventable disease that is caused by Bordetella pertussis bacteria. Pertussis vaccination has been part of the Finnish national vaccine program since 1952. Despite extensive vaccinations, the incidence of pertussis has increased in many countries during the last decades. Large epidemics have been observed also in countries with high vaccine coverage. Inter-individual variation in immune responses is always encountered after vaccination. Low vaccine responses may cause vulnerability to pertussis even straight after vaccination. Reasons for low responses are not fully understood. The innate immune system is responsible for the initial recognition of pathogens and vaccine antigens. The role of innate immunity on pertussis immunity has not been thoroughly investigated. Mannose-binding lectin (MBL) and toll-like receptor 4 (TLR4) are important molecules of the innate immune system and in the recognition of pathogens. Cytokines form a signaling network that have a notable role in immune responses after infections as well as after vaccinations. Single nucleotide polymorphism (SNP) is common in genes encoding these molecules and the polymorphisms have been reported to affect vaccine response after viral and bacterial vaccines. This study investigated the gene polymorphisms of MBL2, TLR4 and interleukin (IL)-10 promoter and their association with vaccine responses after acellular pertussis (aP) vaccination in Finnish adolescents and infants. Cell-mediated immune responses were investigated ten years after the previous pertussis vaccinations in young adults. In addition, the role of MBL deficiency in pertussis infection susceptibility was evaluated. The results of this study show that subjects with TLR4 polymorphism had lower antibody production and persistence after aP vaccination compared with normal allele. A specific SNP in the TLR4 gene was associated with decreased antibody responses and persistence in adolescents after aP booster vaccination. Cell-mediated immune responses were partly detected ten years after the previous vaccination; booster vaccine clearly enhanced the responses. In addition, subjects with IL-10 polymorphism had altered cell-mediated immune responses. MBL deficiency was found to be more frequent in pertussis patients than healthy controls but the polymorphism of MBL2 was not associated with antibody responses after acellular pertussis vaccination. The novel finding of this study was that genetic variation in the innate immune system seems to play a role in altered pertussis vaccine responses as well as in pertussis infection. These new findings enlighten the mechanisms behind the low responses after pertussis vaccination and help to predict risk factors related to this phenomenon.

Nasopharyngeal colonization by pathogenic bacteria: effect of polymorphisms in innate immune genes of young children

Nasopharyngeal bacteria can asymptomatically colonize the nasopharynx of infants and young children but are also associated with the development of respiratory infections and diseases. Such nasopharyngeal bacteria include Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Staphylococcus aureus. The host defense against invading pathogens is largely relies germline-encoded pattern recognition receptors (PRR), which are expressed on the cells of innate immunity, and different cytokines. These include toll-like receptors (TLR), mannose-binding lectin (MBL) and different cytokines such as IL-17A. Single nucleotide polymorphisms (SNP) in these receptors and cytokines have been reported. The aim of this study was to investigate genetic polymorphisms in the genes for TLR2, 3 and 4, MBL as well as for IL-17A and their associations with nasopharyngeal pathogenic bacterial colonization during a two-year follow-up. The study revealed that polymorphisms in TLRs, MBL2 and IL17A are associated with the nasopharyngeal bacterial colonization in young children. Healthy young (2.6 months of age) children with variant types of MBL2, TLR2 R753Q or TLR4 D299G had an increased risk to be colonized by S. pneumonia, S. aureus or M. catarrhalis, respectively. Moreover, variant types of MBL2 in healthy children with might facilitate human rhinovirus (HRV)-induced S. pneumoniae colonization at 2.6 months of age. The polymorphism of TLR4 D299G was shown to be associated with M. catarrhalis colonization throughout the whole two-year follow-up (2.6, 13 and 24 months of age) and also with the bacterial load of this pathogen. Also, the polymorphism of IL17A G152A was shown to be associated with increased risk to be colonized by S. pneumoniae at 13 and 24 months of age. Furthermore, the results suggest that IL17A G152A has an effect on production of serum IL-17A already at young age. In conclusion, the results of this study indicate that polymorphisms in the key PRRs and IL17A seem to play an important role to colonization of S. pneumoniae, M. catarrhalis, and S. aureus in healthy young Finnish children. The nasopharyngeal colonization by these pathogenic bacteria may further promote the development of respiratory infections and may be related to development of asthma and allergy in the later life of children. These findings offer a possible explanation why some children have more respiratory infections than other children and provide a rational basis for future studies in this field.

Fluorescence in situ hybridization of potato somatohaploids and their somatic hybrid donors using two Solanum brevidens specific sequences

Selostus: Perunan somaattisten hybridien ja niiden somatohaploidien fluoresenssi in situ -hybridisaatio Solanum brevidens -lajin spesifisten sekvenssien avulla

Association between protein feeding and reproductive efficiency in the dairy cow : specific emphasis on protein feeding in Finland

Selostus: Lypsylehmien valkuaisruokinnan ja hedelmällisyyden yhteys: kirjallisuustutkimus valkuaisruokinnan vaikutuksista Suomen olosuhteissa