Survival, Replication, and Antibody Susceptibility ofEhrlichia chaffeensisoutside of Host Cells

Abstract

Ehrlichia chaffeensis, an obligate intracellular, tick-transmitted bacterium, is susceptible to antibody-mediated host defense, but the mechanism by which this occurs is not understood. One possible explanation is that antibodies directly access the bacteria in the extracellular environment of the host, perhaps during bacterial intercellular transfer. Accordingly, we investigated whether bacteria could be found outside of host cells during infection. Host cell-free plasma obtained from infected mice was found to contain ehrlichiae, and the host cell-free ehrlichiae readily transferred disease to susceptible SCID recipients. The host cell-free ehrlichiae were found during infection of both immunocompetent BALB/c and immunocompromised BALB/c-scid mice and reached levels as high as 10 8 /ml in plasma during persistent infection in SCID mice. Approximately 10% of the blood-borne bacteria were found outside of host cells. Although it is generally accepted that replication of ehrlichiae occurs only within host cells, the cell-free bacteria were shown to undergo DNA replication and cell division in vitro for 3 to 5 days when incubated at 37°C in plasma. Paradoxically, both infectivity and virulence were lost after 24 h of ex vivo culture. The data indicate that E. chaffeensis is exposed to the extracellular milieu during infection, presumably during intercellular transfer, and reveal that these intracellular bacteria do not require the environment of the host cell for replication. Our findings reveal a possible mechanism by which antibodies can access the intracellular bacteria upon their release into the extracellular milieu and mediate host defense and also have implications for understanding the replication and transmission of this vectorborne pathogen.

Production of IFN-γ by CD4 T Cells Is Essential for Resolving Ehrlichia Infection

“…However, SCID mice were fully susceptible to as few as 10 bacteria, as quantitated by PCR, which suggested that most of the bacteria in the inocula used in the studies were viable. These data were similar to those obtained after inoculation of SCID mice with limiting numbers of E. chaffeensis (24). Thus, data from both models suggest that SCID mice offer little or no resistance to ehrlichia infection.…”

“…Preliminary studies have also revealed the presence of bacteria in the host cell-free plasma of infected mice, as was also observed during E. chaffeensis infection (Ref. 24; data not shown).…”

Socially transmitted gut microbiota protect bumble bees against an intestinal parasite

“…Perhaps in vitro culturing had rendered them noninfectious because bees fed with fresh feces from bees infected with the Gammaproteobacteria became readily infected. A rapid loss of infectivity during in vitro culturing has been described before for bacteria closely associated with their hosts (20,21), including one report for honey bees exposed to an undescribed bacterium referred to as "Bacterium eurydice" (22). Altogether, therefore, the combined results indicate that feeding feces from nest mates leads to the establishment of the microbiota comparable to that present in workers within the source colony and also similar to the microbiota observed in healthy bumble bees in the field.…”

Reinfection withAnaplasma phagocytophilumin BALB/c Mice and Cross-Protection between Two Sympatric Isolates

“…Because there is no evidence that antibodies have direct access to the pathogens inside the host cell, it has been reasoned that they may be exposed to antibodies in the host extracellular milieu, perhaps during intercellular spreading (24). Such a mechanism would not necessarily prevent a reinfection per se but may limit the severity and longevity of ensuing disease.…”