Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model
| Autor: | John H. Moore, Carrie A. Cowardin, David T. Bolick, Gregory A. Buck, Jerrold R. Turner, James K. Roche, Ana M. Lara, Francisco Jose Noronha, Glynis L. Kolling, Cirle A. Warren, Luther A. Bartelt, Edna I. Zaenker, Richard L. Guerrant |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Bacterial Diseases Protozoan Vaccines Physiology animal diseases Priming (immunology) Cryptosporidiosis Pathology and Laboratory Medicine Salmonella Typhi White Blood Cells Mice Salmonella Animal Cells Immune Physiology Medicine and Health Sciences Immune Response Protozoans Innate Immune System biology T Cells lcsh:Public aspects of medicine Cryptosporidium 3. Good health Bacterial Pathogens Vaccination Cryptosporidium parvum Infectious Diseases Medical Microbiology Cytokines Female Dietary Proteins Pathogens Cellular Types Research Article lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 Immune Cells Immunology Microbiology 03 medical and health sciences Immune system Antigen Enterobacteriaceae Immunity parasitic diseases Animals Microbial Pathogens Administration Intranasal Nutrition Blood Cells Bacteria Malnutrition Public Health Environmental and Occupational Health Organisms Cryptosporidium Parvum TLR9 Biology and Life Sciences lcsh:RA1-1270 Cell Biology Molecular Development biology.organism_classification Parasitic Protozoans Diet Mice Inbred C57BL 030104 developmental biology Immune System Developmental Biology |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 10, Iss 7, p e0004820 (2016) |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children. Author Summary Cryptosporidium attributable morbidities in malnourished children are increasingly recognized. Exactly how malnutrition interferes with host mucosal immunity to diarrheal pathogens and mucosal vaccine responses remains unclear. Dissecting these interactions in an experimental model of cryptosporidiosis can uncover new insights into novel therapeutic approaches against a pathogen for which effective therapies and vaccines are currently unavailable. We demonstrate that although malnutrition diminishes baseline (primary) Th1-type mucosal immunity these deficits can be partially overcome via non-specific mucosal strategies (S. Typhi and CpG) and completely restored after a sub-clinical (low-dose) exposure to viable C. parvum. These results add insight into preventive strategies to help alleviate Cryptosporidium-specific diarrhea in children in low-resource settings and abrogate prolonged post-infection sequelae. |
| Databáze: | OpenAIRE |
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