RESUMO
Periparturient relaxation of immunity (PPRI) to secondary infection with nematodes is believed to have a nutritional basis due to differential partitioning of scarce nutrient resources, particularly protein, to reproductive rather than immune functions. At times of protein scarcity, an increase in protein supply has been reported to assuage this phenomenon. The Nippostrongylus brasiliensis reinfected lactating rat model is now being utilized to investigate the immune reactions underlying the modifying role of dietary protein on PPRI. Herein, we demonstrate that lactating rats reinfected with N. brasiliensis under high protein (HP) dietary conditions exhibit decreased worm burdens and reduced colon egg counts compared to their low protein (LP) counterparts. These reductions correlated with increased mastocytosis and greater goblet cell hyperplasia. Additionally, the local antibody profile revealed that HP reinfected lactating rats developed a stronger antigen specific IgG2b response earlier in infection in comparison with their LP counterparts. Our study provides evidence that increased dietary protein content reduces the PPRI to N. brasiliensis re-infection in the lactating rat through improved mucosal immune responses.
Assuntos
Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/farmacologia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Colo/parasitologia , Feminino , Células Caliciformes/imunologia , Mastócitos/imunologia , Contagem de Ovos de Parasitas , RatosRESUMO
Nippostrongylus brasiliensis, the rodent hookworm, is a commonly used model of gastrointestinal nematode infection. This parasite, hookworms and several livestock nematode parasites of importance secrete distinct forms of acetylcholinesterases (AChE) that have been ascribed a putative parasite protective function. We tested the hypothesis that vaccination with the secreted enzyme would be deleterious to the parasite. Rats were immunised with a recombinant AChE isoform B via the subcutaneous, intra-peritoneal and intra-nasal routes using different adjuvants dependent on the mode of delivery and subsequently challenged with N. brasiliensis. Rats immunised via the subcutaneous and intra-nasal routes showed a modest but significant decrease in egg output of between 23 and 48%. This was mirrored by differences in the titre of specific antibody isotypes in the serum and mucosa following infection and serum from vaccinated animals was demonstrated to inhibit the activity of recombinant and native AChE. The utility of this model for future development of hookworm and veterinary nematode vaccines is discussed.
Assuntos
Acetilcolinesterase/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/prevenção & controle , Vacinação , Animais , Anticorpos Anti-Helmínticos/sangue , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Masculino , Contagem de Ovos de Parasitas , Ratos , Ratos WistarRESUMO
This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.