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Among human and nonhuman animals, the prevalence and intensity of infection typically is higher in males than females and may reflect differences in exposure as well as susceptibility to pathogens. Elevated immunity among females is a double-edged sword in which it is beneficial against infectious diseases but is detrimental in terms of increased development of autoimmune diseases. The present book critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection. It emphasizes the value of examining responses in both males and females to improve our understanding about host-pathogen interactions in both sexes. The contributors are experts in their specific disciplines which range from microbiology and immunology to genetics, pathology, and evolutionary biology. The book aims at bringing insight to the treatment and management of infectious diseases; it delineates areas where knowledge is lacking and highlights future avenues of research.

Successful pregnancy is dependent on many dynamic immunological events that occur at the maternal–fetal interface. While the trophoblast initiates implantation through the uterine wall, maternal immune mechanisms limit the extent to which the decidua is invaded by the placenta without disrupting pregnancy. Immunological reactions are not observed at the maternal–fetal interface. Pregnancy-induced modulation of systemic maternal immunity results in amelioration of certain autoimmune diseases and exacerbation of some infectious diseases. Alteration of immunological function during pregnancy in some circumstances might facilitate congenital transmission of certain pathogens. In other circumstances, the immune reactions induced by pathogens might result in disruption of pregnancy. These complex interactions are discussed in the context of a number of diseases caused by infection with taxonomically diverse protozoan parasites, nematodes, and cestodes.

Charles Darwin contemplated the evolution of diversity within species in his book, On the Origin of Species. Darwin noted that there are profound differences between the sexes of a single species that evolve through a process he termed sexual selection. We propose that consideration of the adaptive significance as well as the mechanisms underlying why males and females respond differently to infection is fundamental for progress in infectious disease research. Future studies must consider not only the role that hormones play in modulating responses to infection, but also how genes, including sex chromosomal genes, impact responses to infection differentially between the sexes. Finally, by illustrating that sex and reproductive status impact responses to infection it is demonstrated that these factors might also influence responses to therapeutic treatments, including vaccines.

Toxoplasma gondii, by all conceivable ecological and epidemiological measurements and analysis, has to be regarded as an extremely successful parasite. It has been found in high incidence in most warm blooded vertebrates and has a generally global distribution. Approximately 30% of the world’s human population is infected, although the prevelance varies markedly from country to country (Jackson and Hutchison 1989).

We have recently established that vertical disease transmission from the mother to the foetus, as in humans and sheep, only occurs in BALB/c mice infected with Toxoplasma gondii for first time during pregnancy. Thus a previous infection generally gives life long immunity, as ideally, would an effective vaccine. Of three major fractions harvested from RH strain tachyzoites (membrane, soluble and excretory/secretory) the soluble fraction was found the most effective in reducing mortality and cyst burdens in adult mice. Further studies indicated that the choice of adjuvant could enhance this effect. Entrapment within non-ionic surfactant vesicles (NISV), but not Freund’s Complete Adjuvant, significantly enhanced the protection afforded by soluble antigen to adult mice as well as greatly increasing the T cell specific proliferative response, IFN-γ production and antibody levels. NISV are safe, stable, and inexpensive and promote TH1 and CD8+ lymphocyte activation. In BALB/c dams vaccinated with NISV entrapped soluble antigen and infected on day 12 of pregnancy with 20 tissue cysts of T. gondii (RRA strain), congenital infection was reduced from a control level of 50% to 12% in surviving offspring and foetal death from 50% to nil. The identification of protective antigens in the soluble fraction is well advanced.

The murine chromosome 1 gene Lsh/Ity/Bcg gene was identified nearly 20 years ago for its role in controlling the early phase of infection with Salmonella typhimurium and Leishmania donovani, and later as a major regulator of mycobacterial infections including Mycobacterium bovis BCG. Functional macrophage studies have shown that Lsh regulates macrophage priming activation for antimicrobial activity via the TNF-α dependent production of reactive nitrogen intermediates. Differential regulation of TNF-α is observed in bone marrow-derived macrophages from Lsh congenic mouse strains in response to both lipopolysaccharide and mycobacterial lipoarabinomannan, and when macrophages are plated onto the extracellular matrix proteins fibronectin and fibrinogen. The former accounts for the induction Lsh resistance mechanism by the infecting microorganism. The latter explains differential Lsh gene expression in macrophages in different tissue sites in vivo, in particular in the viscera versus the skin. Since macrophages are an important host cell in Toxoplasma gondii infection, and T. gondii is known to elicit a strong TNF-α response, we thought it would be of interest to examine this infection in Lsh congenic mouse strains.