عنوان

The ecology of anthrax and coinfection trade-offs from an immunological perspective:

شماره

TL96z0995b

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

The ecology of anthrax and coinfection trade-offs from an immunological perspective:

نام عام مواد

[Thesis]

نام نخستين پديدآور

Cizauskas, Carrie Ann

عنوان اصلي به قلم نويسنده ديگر

seasonal aspects of host susceptibility

نام ساير پديدآوران

Getz, Wayne M

نام ناشر، پخش کننده و غيره

UC Berkeley

تاریخ نشرو بخش و غیره

2013

کسي که مدرک را اعطا کرده

UC Berkeley

امتياز متن

2013

متن يادداشت

Seasonal fluctuations in infectious disease incidence are common, and have been observed for many infectious agents. Immune condition can also change seasonally due to such pathogen fluctuations, a well as to changes in other stress-inducing and immunomodulatory factors such as reproduction and lactation. In addition, most vertebrate hosts are concurrently infected with multiple pathogens, and such coinfections can interact with each other, with the immune system, and with other physiological factors to affect both the individual hosts and population dynamics. While many studies regarding the effects of coinfections and immune trade-offs have been conducted in laboratory settings, similar studies in wildlife are as yet very rare. Fewer studies have been conducted regarding disease and immune seasonality, as these are difficult to model in laboratory settings and require difficult, longitudinal studies in natural systems. In addition, most research regarding disease seasonality in natural systems that has been done has focused on the impacts of abiotic factors on pathogen and vector survival and abundance, or on population-wide dynamics, rather than on physiological mechanisms of host susceptibility. To fully understand the ecology of infectious diseases and the reasons for disease outbreaks, it is necessary to extend laboratory studies into natural hosts in natural systems, as well as to extend wildlife studies to incorporate the complex interactions between environmental, physiological, and coinfection factors. My dissertation research thus focused on the ecological immunology of infectious disease in a natural system, from physiological, seasonal, and coinfection perspectives. I examined the ability of plains zebra (Equus quagga), springbok (Antidocas marsupialis), and African elephant (Loxodonta africana) to respond immunologically to regular anthrax outbreaks in an endemic anthrax system (Etosha National Park, ENP, Namibia). I also examined how zebra and springbok macroparasite coinfections varied with and affected changes in immune parameters, stress, reproductive hormone levels, and seasonal timing of anthrax outbreaks. Despite the fact that anthrax is an ancient disease known to affect wildlife, livestock, and humans on nearly every continent, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis, the causative agent of anthrax. Thus, I worked to determine the extent to which natural anthrax hosts can fight off sublethal anthrax doses via adaptive immunity. I used enzyme-linked immunosorbent assays, and developed new assay mensuration rules to determine serum antibody titers against the anthrax protective antigen (PA) toxin, an important, potentially protective aspect of adaptive immunity against anthrax. I found that more than 60% of all zebra, up to 15% of springbok, and up to 50% of elephants had measurable anti-PA antibody titers, indicating that these hosts experience and survive sublethal anthrax infections, likely encounter more anthrax in the wet season compared to in the dry, and can partially booster their immunity to B. anthracis over time. Most pathogen-pathogen interactions occur indirectly through the host immune system, and are particularly strong in mixed micro-macroparasite infections because of the strong immunomodulatory effects of helminth parasites. As pathogen transmission changes with season, host immunity may be more strongly influenced by coinfection immunomodulatory effects than by external factors such as changing dietary and demographic patterns. I thus examined the seasonality of immune functionality, pathogen infectivity, and interactions between concurrent infections and immunity in wild zebra in ENP, a system with strongly seasonal patterns of gastrointestinal (GI) helminth infection intensity and concurrent anthrax outbreaks. I found evidence that wet seasons in ENP are characterized by Th2-type immune skewing driven by GI helminth infections, and that these trade-offs make hosts less capable of mounting effective Th1-type immune responses against anthrax infections at this time. I also found evidence that coinfections and immune tradeoffs affect long-term host survival, and that GI parasites likely exert more selection pressure on zebra hosts than do ectoparasites and anthrax, but may actually be a stabilizing force in this host-pathogen system. Stress and reproductive hormones can modulate each other and the immune system, and can affect disease incidence. Pathogens can also cause host stress, as well as exploit host niches exposed by stress and reproductive hormone-induced immunomodulation. Therefore, I examined seasonal correlations between host stress, reproduction, and GI parasite coinfections in zebra and springbok in ENP. All three macroparasites examined (strongyle helminths, Strongyloides helminths, and Eimeria coccidia) had strongly seasonal signals, with hosts experiencing the highest parasite infection intensities during times of highest rainfall and highest anthrax outbreaks. Strongyles appeared to be perhaps most potent immunomodulating pathogen in this system, influencing zebra immune responses to anthrax and susceptibility to tick infestations, as well as springbok susceptibility to Strongyloides infections. However, helminths were mostly negatively associated with stress hormone concentrations and Eimeria had almost no interaction with stress, indicating that most hosts have developed tolerance toward even high macroparasite loads. Stress hormone concentrations were nearly uniformly higher in drier times than in wetter ones, and were positively affected by estrogen concentrations in females, likely indicating that seasonal nutritional and water stressors, as well as pregnancy stress during the dry season trumped the effects of pathogen infection intensities in causing host stress. In addition, adult animals had higher stress levels than did yearlings, despite yearlings being the largest aggregator of parasites, corroborating the idea that reproductive status is more influential in determining host stress than are pathogens in this system and that mechanisms of tolerance to GI parasites are substantial. In conclusion, my results indicate that GI parasites play a large role in determining host immune status and susceptibility to micro- and macroparasite coinfections. While ENP herbivores survive anthrax infections with regularity, host immunomodulation by GI parasites likely determines whether a host will mount a successful immune response against this potentially deadly pathogen. GI parasites modulate these coinfection interactions despite causing hosts little direct stress; thus, these coinfection interactions likely take place mostly through direct immunomodulatory effects rather than indirectly through host pathology, nutritional depletion, and other potentially stress-inducing sequelae. ENP zebra and springbok appear to be tolerant of their macroparasite loads, trading off parasite immunomodulatory and pathological effects in favor of balancing resource allocation toward reproductive efforts.

مستند نام اشخاص تاييد نشده

Cizauskas, Carrie Ann

مستند نام اشخاص تاييد نشده

Getz, Wayne M

مستند نام تنالگان تاييد نشده

UC Berkeley

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y